N*1*-[7-(4-Dimethylamino-phenyl)-[1,6]naphthyridin-5-yl]-butane-1,4-diamine

ID: ALA282342

PubChem CID: 10308737

Max Phase: Preclinical

Molecular Formula: C20H25N5

Molecular Weight: 335.46

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CN(C)c1ccc(-c2cc3ncccc3c(NCCCCN)n2)cc1

Standard InChI:  InChI=1S/C20H25N5/c1-25(2)16-9-7-15(8-10-16)18-14-19-17(6-5-13-22-19)20(24-18)23-12-4-3-11-21/h5-10,13-14H,3-4,11-12,21H2,1-2H3,(H,23,24)

Standard InChI Key:  SBGMPUIVPOGTGN-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 25 27  0  0  0  0  0  0  0  0999 V2000
   18.2884   -1.7175    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5807   -1.2990    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.5860   -0.4733    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8623   -1.7046    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8551   -2.5267    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1365   -2.9323    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4290   -2.5138    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4341   -1.6881    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1526   -1.2825    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7104   -2.9194    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7032   -3.7415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9847   -4.1470    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9775   -4.9692    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.2590   -5.3747    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5514   -4.9562    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5587   -4.1342    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2772   -3.7285    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2823   -2.9028    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5748   -2.4843    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.8562   -2.8900    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1487   -2.4715    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4302   -2.8771    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7226   -2.4586    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0041   -2.8641    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.0009   -2.4973    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  4  9  1  0
  7 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 12 17  2  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  1  0
 18 25  2  0
 10 25  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA282342

   N1-(7-(4-(dimethylamino)phenyl)-1,6-naphthyridin-5-yl)butane-1,4-diamine

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: 335.46

Molecular Weight (Monoisotopic): 335.2110

AlogP: 3.51

#Rotatable Bonds: 7

Polar Surface Area: 67.07

Molecular Species: BASE

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 10.20

CX LogP: 2.90

CX LogD: 0.30

Aromatic Rings: 3

Heavy Atoms: 25

QED Weighted: 0.65

Np Likeness Score: -1.13

References

1. Cywin CL, Zhao BP, McNeil DW, Hrapchak M, Prokopowicz AS, Goldberg DR, Morwick TM, Gao A, Jakes S, Kashem M, Magolda RL, Soll RM, Player MR, Bobko MA, Rinker J, DesJarlais RL, Winters MP..  (2003)  Discovery and SAR of novel Naphthyridines as potent inhibitors of spleen tyrosine kinase (SYK).,  13  (8): [PMID:12668002] [10.1016/s0960-894x(03)00163-x]

2. Xie HZ, Li LL, Ren JX, Zou J, Yang L, Wei YQ, Yang SY..  (2009)  Pharmacophore modeling study based on known spleen tyrosine kinase inhibitors together with virtual screening for identifying novel inhibitors.,  19  (7): [PMID:19254842] [10.1016/j.bmcl.2009.02.049]

3. Bamborough P, Drewry D, Harper G, Smith GK, Schneider K..  (2008)  Assessment of chemical coverage of kinome space and its implications for kinase drug discovery.,  51  (24): [PMID:19035792] [10.1021/jm8011036]

4. Singh R, Masuda ES, Payan DG..  (2012)  Discovery and development of spleen tyrosine kinase (SYK) inhibitors.,  55  (8): [PMID:22257213] [10.1021/jm201271b]

5. Hisamichi, Hiroyuki H and 10 more authors.  2005-08-15  Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure-activity relationships of pyrimidine-5-carboxamide derivatives.  [PMID:15990316]

6. Wang, Wei-Ya; Hsieh, Pei-Wen; Wu, Yang-Chang and Wu, Chin-Chung.  2007-08-15  Synthesis and pharmacological evaluation of novel beta-nitrostyrene derivatives as tyrosine kinase inhibitors with potent antiplatelet activity.  [PMID:17601492]

7. Hirabayashi, Akihito A and 10 more authors.  2008-10-15  Structure-activity relationship studies of imidazo[1,2-c]pyrimidine derivatives as potent and orally effective Syk family kinases inhibitors.  [PMID:18823784]

8. 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]

9. Coffey, Greg G and 12 more authors.  2012-02  Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis.  [PMID:22040680]

10. Lau, Ken S KS and 5 more authors.  2012  BAY61-3606 affects the viability of colon cancer cells in a genotype-directed manner.  [PMID:22815993]

11. Lucas, Matthew C MC and 12 more authors.  2012-12-13  Rational design of highly selective spleen tyrosine kinase inhibitors.  [PMID:23151054]

12. Kaur, Maninder M, Singh, Manjinder M and Silakari, Om O.  2013-09  Inhibitors of switch kinase 'spleen tyrosine kinase' in inflammation and immune-mediated disorders: a review.  [PMID:23917087]

13. Lucas, Matthew C MC and 22 more authors.  2014-03-27  Using ovality to predict nonmutagenic, orally efficacious pyridazine amides as cell specific spleen tyrosine kinase inhibitors.  [PMID:24520947]

14. Currie, Kevin S KS and 16 more authors.  2014-05-08  Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase.  [PMID:24779514]

15. Coffey, Greg G and 8 more authors.  2014-12  The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer.  [PMID:25253883]

16. Thoma, Gebhard G and 9 more authors.  2015-02-26  Discovery and profiling of a selective and efficacious Syk inhibitor.  [PMID:25633741]

17. Hoemann, Michael M and 11 more authors.  2016-11-15  Synthesis and optimization of furano[3,2-d]pyrimidines as selective spleen tyrosine kinase (Syk) inhibitors.  [PMID:27789138]

18. Lam, Betty B and 21 more authors.  2016-12-15  Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK).  [PMID:27839918]

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

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. Hayashi, Hiroaki H and 9 more authors.  2018-07  TAS05567, a Novel Potent and Selective Spleen Tyrosine Kinase Inhibitor, Abrogates Immunoglobulin-Mediated Autoimmune and Allergic Reactions in Rodent Models.  [PMID:29728446]

22. Barker, Michael D MD and 11 more authors.  2018-11-15  Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease.  [PMID:30249354]

23. Choi, Min Jung MJ and 8 more authors.  2018-12-15  Design, synthesis, and biological evaluation of novel aminopyrimidinylisoindolines as AXL kinase inhibitors.  [PMID:30340900]

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. Blomgren, Peter and 21 more authors.  2020-04-09  Discovery of Lanraplenib (GS-9876): A Once-Daily Spleen Tyrosine Kinase Inhibitor for Autoimmune Diseases.  [PMID:32292557]

26. Fromont, Christophe and 33 more authors.  2020-07-09  Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesity in Vivo Mouse Model.  [PMID:32433887]

27. Kawatkar, Sameer P and 20 more authors.  2020-09-15  Identification of a novel series of azabenzimidazole-derived inhibitors of spleen tyrosine kinase.  [PMID:32721854]

Source

Source(1):

• Scientific Literature