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(Z)-4-(2-Amino-4-oxo-1H-imidazol-5(4H)-ylidene)-2-(3,4-dimethoxyphenyl)-4,5,6,7-tetrahydropyrrolo[2,3-c]azepin-8(1H)-one

ID: ALA1947252

PubChem CID: 136020049

Max Phase: Preclinical

Molecular Formula: C19H19N5O4

Molecular Weight: 381.39

Molecule Type: Small molecule

This compound is available for customization.

Associated Items:

Names and Identifiers

Canonical SMILES:  COc1ccc(-c2cc3c([nH]2)C(=O)NCC/C3=C2/NC(N)=NC2=O)cc1OC

Standard InChI:  InChI=1S/C19H19N5O4/c1-27-13-4-3-9(7-14(13)28-2)12-8-11-10(15-18(26)24-19(20)23-15)5-6-21-17(25)16(11)22-12/h3-4,7-8,22H,5-6H2,1-2H3,(H,21,25)(H3,20,23,24,26)/b15-10-

Standard InChI Key:  FWOPNZXELLFNIM-GDNBJRDFSA-N

Molfile:  

     RDKit          2D

 28 31  0  0  0  0  0  0  0  0999 V2000
   26.3721    0.5449    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.0172    1.2877    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.2151    1.4695    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.0154   -0.1964    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   25.2117   -0.3778    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.5682    0.1426    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.5674    0.9552    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7941    1.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.3196    0.5455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7954   -0.1120    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   25.0259   -1.1823    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   25.5087    2.9495    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.0252    3.6180    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.2398    3.3635    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.2405    2.5377    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.9844    2.1910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.5706    3.8458    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.3344    2.9585    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.4938    0.5448    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.0807    1.2592    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2557    1.2587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8448    0.5421    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2608   -0.1756    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.0844   -0.1715    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.0190    0.5402    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.6024    1.2548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8532   -0.8931    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   20.0275   -0.8968    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
  2  3  1  0
 15 16  1  0
  1  4  1  0
 14 17  1  0
  5  6  1  0
 12 18  2  0
  7  8  1  0
  9 19  1  0
  8  9  2  0
 19 20  2  0
  9 10  1  0
 20 21  1  0
 10  6  1  0
 21 22  2  0
  7  3  1  0
 22 23  1  0
  5 11  2  0
 23 24  2  0
 24 19  1  0
  3 16  2  0
 22 25  1  0
 16 12  1  0
 25 26  1  0
  4  5  1  0
 23 27  1  0
  6  7  2  0
 27 28  1  0
M  END

Alternative Forms

  1. Parent:

    ALA1947252

    ---

Associated Targets(Human)

CHEK1 Tchem Serine/threonine-protein kinase Chk1 (6846 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CHEK2 Tchem Serine/threonine-protein kinase Chk2 (4015 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: 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

Biocomponents

Calculated Properties

Molecular Weight: 381.39Molecular Weight (Monoisotopic): 381.1437AlogP: 0.99#Rotatable Bonds: 3
Polar Surface Area: 130.83Molecular Species: NEUTRALHBA: 6HBD: 4
#RO5 Violations: HBA (Lipinski): 9HBD (Lipinski): 5#RO5 Violations (Lipinski):
CX Acidic pKa: 13.85CX Basic pKa: 4.28CX LogP: -0.44CX LogD: -0.44
Aromatic Rings: 2Heavy Atoms: 28QED Weighted: 0.59Np Likeness Score: 0.58

References

1. Saleem RS, Lansdell TA, Tepe JJ..  (2012)  Synthesis and evaluation of debromohymenialdisine-derived Chk2 inhibitors.,  20  (4): [PMID:22285028] [10.1016/j.bmc.2011.12.054]
2. Akunuri R, Vadakattu M, Bujji S, Veerareddy V, Madhavi YV, Nanduri S..  (2021)  Fused-azepinones: Emerging scaffolds of medicinal importance.,  220  [PMID:33901899] [10.1016/j.ejmech.2021.113445]
3. Feldman, Richard I RI and 17 more authors.  2005-05-20  Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1.  [PMID:15772071]
4. Conchon, Elisabeth E and 6 more authors.  2008-02  Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of pyrrolo[3,4-a]carbazole-1,3-diones, pyrrolo[3,4-c]carbazole-1,3-diones, and 2-aminopyridazino[3,4-a]pyrrolo[3,4-c]carbazole-1,3,4,7-tetraone.  [PMID:17502122]
5. Hugon, Bernadette B and 8 more authors.  2007-09-01  Synthesis and biological activities of isogranulatimide analogues.  [PMID:17582773]
6. Conchon, Elisabeth E, Anizon, Fabrice F, Aboab, Bettina B and Prudhomme, Michelle M.  2007-09-20  Synthesis and biological activities of new checkpoint kinase 1 inhibitors structurally related to granulatimide.  [PMID:17722905]
7. Garbaccio, Robert M RM and 22 more authors.  2007-11-15  Synthesis and evaluation of substituted benzoisoquinolinones as potent inhibitors of Chk1 kinase.  [PMID:17900896]
8. Conchon, Elisabeth E and 6 more authors.  2008-04-15  Synthesis, checkpoint kinase 1 inhibitory properties and in vitro antiproliferative activities of new pyrrolocarbazoles.  [PMID:18321713]
9. Zarrinkar, Patrick P PP and 15 more authors.  2009-10-01  AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).  [PMID:19654408]
10. Anderson, Victoria E and 10 more authors.  2011-01-15  CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors.  [PMID:21239475]
11. Reader, John C JC and 27 more authors.  2011-12-22  Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.  [PMID:22111927]
12. Lainchbury, Michael and 15 more authors.  2012-11-26  Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.  [PMID:23082860]
13. Edupuganti, Ramakrishna R and 9 more authors.  2017-05-01  Discovery of a potent inhibitor of MELK that inhibits expression of the anti-apoptotic protein Mcl-1 and TNBC cell growth.  [PMID:28351607]
14. Farag, Ahmed Karam AK and 5 more authors.  2017-12-01  Novel LCK/FMS inhibitors based on phenoxypyrimidine scaffold as potential treatment for inflammatory disorders.  [PMID:29107425]
15. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]
16. Narayan, Satya S and 7 more authors.  2019-01-01  ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.  [PMID:30384048]
17. Tong, Lexian L and 12 more authors.  2019-07-01  Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies.  [PMID:30986571]

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