N4'-(cyclopropylmethyl)-6-methyl-N3-(3-(piperidin-1-yl)phenyl)biphenyl-3,4'-dicarboxamide

ID: ALA1964275

Cas Number: 1093222-29-7

PubChem CID: 57394915

Max Phase: Preclinical

Molecular Formula: C30H33N3O2

Molecular Weight: 467.61

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1ccc(NC(=O)c2cccc(N3CCCCC3)c2)cc1-c1ccc(C(=O)NCC2CC2)cc1

Standard InChI:  InChI=1S/C30H33N3O2/c1-21-8-15-26(32-30(35)25-6-5-7-27(18-25)33-16-3-2-4-17-33)19-28(21)23-11-13-24(14-12-23)29(34)31-20-22-9-10-22/h5-8,11-15,18-19,22H,2-4,9-10,16-17,20H2,1H3,(H,31,34)(H,32,35)

Standard InChI Key:  DANPUZSWWCDWEM-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 35 39  0  0  0  0  0  0  0  0999 V2000
   -2.8514    1.3125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8526    0.4852    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1378    0.0723    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4213    0.4856    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4242    1.3162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1396    1.7253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7143    1.7301    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0020    1.3185    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7144    1.7330    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7117    2.5589    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0093    2.9685    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7188    2.5517    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4359    2.9595    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4302    1.3229    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.1433    1.7377    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8592    1.3276    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5674    0.0732    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2815    0.4863    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5680   -0.7518    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2828   -1.1637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2835   -1.9887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6932   -2.6997    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8682   -2.7003    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8583    0.5031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5732    0.0930    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2873    0.5079    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2820    1.3372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5664    1.7435    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5755   -0.7320    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.8628   -1.1432    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8631   -1.9646    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5769   -2.3790    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2921   -1.9657    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2934   -1.1381    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1406    2.5627    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 15 16  1  0
  8  9  1  0
  2 17  1  0
  4  5  1  0
 17 18  2  0
  9 10  2  0
 17 19  1  0
  2  3  1  0
 19 20  1  0
 10 11  1  0
 20 21  1  0
 22 21  1  0
 23 22  1  0
 21 23  1  0
  5  6  2  0
 11 12  2  0
 12  7  1  0
 16 24  2  0
  5  7  1  0
 24 25  1  0
  6  1  1  0
 25 26  2  0
 12 13  1  0
 26 27  1  0
  1  2  2  0
 27 28  2  0
 28 16  1  0
  9 14  1  0
 25 29  1  0
 29 30  1  0
  3  4  2  0
  7  8  2  0
 14 15  1  0
 29 34  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 34  1  0
 15 35  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA1964275

   [1,1'-Biphenyl]-4-carboxamide, N-(cyclopropylmethyl)-2'-methyl-5'-[[3-(1-piperidinyl)benzoyl]amino]-

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: 467.61

Molecular Weight (Monoisotopic): 467.2573

AlogP: 6.04

#Rotatable Bonds: 7

Polar Surface Area: 61.44

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 4.22

CX LogP: 6.04

CX LogD: 6.04

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.45

Np Likeness Score: -1.37

References

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2. Simon Townson and Suzanne Gokool. GlaxoSmithKline Published Kinase Inhibitor Set 2 Onchocerca lienalis Screening Data,  [10.6019/CHEMBL3988181]

3. Zhu, Gui-Dong GD and 19 more authors.  2006-07-01  Discovery and SAR of oxindole-pyridine-based protein kinase B/Akt inhibitors for treating cancers.  [PMID:16644221]

4. Heerding, Dirk A DA and 27 more authors.  2008-09-25  Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.  [PMID:18800763]

5. Hall, Matthew D and 8 more authors.  2009-05-28  Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells.  [PMID:19397322]

6. Okuzumi, Tatsuya and 6 more authors.  2009-07  Inhibitor hijacking of Akt activation.  [PMID:19465931]

7. McHardy, Tatiana and 17 more authors.  2010-03-11  Discovery of 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as selective, orally active inhibitors of protein kinase B (Akt).  [PMID:20151677]

8. Blake, James F JF and 15 more authors.  2010-10-01  Discovery of pyrrolopyrimidine inhibitors of Akt.  [PMID:20810279]

9. Kim, Mi-hyun MH and 6 more authors.  2011-03-15  Structure based design and syntheses of amino-1H-pyrazole amide derivatives as selective Raf kinase inhibitors in melanoma cells.  [PMID:21353571]

10. Kim, Hyangmi; Kim, Minjung; Lee, Junghun; Yu, Hana and Hah, Jung-Mi.  2011-11-15  Syntheses of phenylpyrazolodiazepin-7-ones as conformationally rigid analogs of aminopyrazole amide scaffold and their antiproliferative effects on cancer cells.  [PMID:22014755]

11. Pireddu, Roberta and 10 more authors.  2012-06-01  Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2).  [PMID:23275831]

12. Addie, Matt M and 21 more authors.  2013-03-14  Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases.  [PMID:23394218]

13. Cheng, Hengmiao H and 12 more authors.  2013-05-01  Structure-based design, SAR analysis and antitumor activity of PI3K/mTOR dual inhibitors from 4-methylpyridopyrimidinone series.  [PMID:23506825]

14. Brown, Andrew and 8 more authors.  2013-05-09  Monocarbonyl curcumin analogues: heterocyclic pleiotropic kinase inhibitors that mediate anticancer properties.  [PMID:23550937]

15. Dumble, Melissa M and 13 more authors.  2014  Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor.  [PMID:24978597]

16. Ye, Qing Q and 14 more authors.  2015-03-01  Synthesis and biological evaluation of 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3β inhibitors and neuroprotective agents.  [PMID:25662701]

17. Lapierre, Jean-Marc JM and 19 more authors.  2016-07-14  Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor.  [PMID:27305487]

18. Sugimoto, Yasuro Y and 8 more authors.  2017-04-01  Novel pyrrolopyrimidines as Mps1/TTK kinase inhibitors for breast cancer.  [PMID:28259529]

19. Liu, Yang Y and 10 more authors.  2017-09-29  Structural optimization elaborates novel potent Akt inhibitors with promising anticancer activity.  [PMID:28704757]

20. 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]

21. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]

22. Gao, Jun-Bo JB and 8 more authors.  2018-04-27  Isolation, Characterization, and Structure-Activity Relationship Analysis of Abietane Diterpenoids from Callicarpa bodinieri as Spleen Tyrosine Kinase Inhibitors.  [PMID:29578342]

23. Zhang, Daoguang D and 5 more authors.  2018-08-01  Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant.  [PMID:30151089]

24. 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]

25. Zha, Gao-Feng; Rakesh, K P; Manukumar, H M; Shantharam, C S and Long, Sihui.  2019-01-15  Pharmaceutical significance of azepane based motifs for drug discovery: A critical review.  [PMID:30469042]

26. Zhan, Wenhu W and 9 more authors.  2019-07-07  Discovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors.  [PMID:31301565]

27. Kumar, Jetta Sandeep and 12 more authors.  2020-09-01  Rosuvastatin based novel 3-substituted isocoumarins / 3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents.  [PMID:32599323]

Source

Source(2):

• Scientific Literature
• Published Kinase Inhibitor Set 2