N-((3S,4S)-3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)tetrahydro-2H-pyran-4-yl)acrylamide

ID: ALA4514636

Cas Number: 1707289-21-1

PubChem CID: 91885617

Product Number: F414033, Order Now?

Max Phase: Phase

Molecular Formula: C24H24Cl2N4O4

Molecular Weight: 503.39

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Fisogatinib | BLU-111362 | BLU-554 | BLU111362 | X-439161 | X439161 | BLU-554|Fisogatinib|1707289-21-1|N-((3S,4S)-3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)tetrahydro-2H-pyran-4-yl)acrylamide|BLU554|BLU111362|Fisogatinib [INN]|Fisogatinib [USAN]|BLU554(Fisogatinib)|X439161|BLU-111362|5Q7R99CKV2|BLU 554|X-439161|2-Propenamide, N-((3S,4S)-3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl)amino)tetrahydro-2H-pyran-4-yl)-|N-[(3S,4S)-3-{[6-(2,6-Dichloro-3,5-dimethoxyphenyl)qShow More⌵

Canonical SMILES:  C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1

Standard InChI:  InChI=1S/C24H24Cl2N4O4/c1-4-20(31)28-16-7-8-34-12-17(16)30-24-27-11-14-9-13(5-6-15(14)29-24)21-22(25)18(32-2)10-19(33-3)23(21)26/h4-6,9-11,16-17H,1,7-8,12H2,2-3H3,(H,28,31)(H,27,29,30)/t16-,17+/m0/s1

Standard InChI Key:  MGZKYOAQVGSSGC-DLBZAZTESA-N

Molfile:  

     RDKit          2D

 34 37  0  0  0  0  0  0  0  0999 V2000
    2.0745    2.3296    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3600    1.9171    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3600    1.0921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0745    0.6795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7889    1.0921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7889    1.9171    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6455    2.3296    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.3599    3.5671    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0744    3.1546    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.0745   -0.1455    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    3.5034   -0.1455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5034    0.6795    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.6455    0.6795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6455   -0.1455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0689    1.0921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7834    0.6795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7834   -0.1455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0689   -0.5580    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4979    1.0921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2123    0.6795    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2123   -0.1455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4979   -0.5580    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9474   -0.5200    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6393   -0.0707    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2880    1.2025    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0231    0.8280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0663    0.0041    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3744   -0.4452    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5961    0.7532    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4176   -1.2691    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1320   -1.6816    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.8465   -1.2691    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1320   -2.5066    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.8465   -2.9191    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  2  0
  3  4  1  0
  4  5  2  0
  5  6  1  0
  1  6  2  0
  8  9  1  0
  1  9  1  0
  2  7  1  0
 11 12  1  0
  4 10  1  0
  5 12  1  0
 13 14  1  0
  3 13  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 15 13  2  0
 18 14  2  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 19 16  1  0
 22 17  1  0
 21 23  1  0
 24 23  1  1
 25 26  1  0
 26 27  1  0
 27 28  1  0
 25 29  1  0
 28 24  1  0
 24 29  1  0
 28 30  1  1
 30 31  1  0
 31 32  2  0
 31 33  1  0
 33 34  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA4514636

   Fisogatinib (BLU-554)

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: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 503.39

Molecular Weight (Monoisotopic): 502.1175

AlogP: 4.49

#Rotatable Bonds: 7

Polar Surface Area: 94.60

Molecular Species: NEUTRAL

HBA: 7

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 13.78

CX Basic pKa: 3.79

CX LogP: 3.86

CX LogD: 3.86

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.46

Np Likeness Score: -0.14

References

1. Lin X, Yosaatmadja Y, Kalyukina M, Middleditch MJ, Zhang Z, Lu X, Ding K, Patterson AV, Smaill JB, Squire CJ..  (2019)  Rotational Freedom, Steric Hindrance, and Protein Dynamics Explain BLU554 Selectivity for the Hinge Cysteine of FGFR4.,  10  (8): [PMID:31413803] [10.1021/acsmedchemlett.9b00196]

2. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

3. Unpublished dataset, 

4. Pan C, Nie W, Wang J, Du J, Pan Z, Gao J, Lu Y, Che J, Zhu H, Dai H, Chen B, He Q, Dong X..  (2021)  Design, synthesis and biological evaluation of quinazoline derivatives as potent and selective FGFR4 inhibitors.,  225  [PMID:34488024] [10.1016/j.ejmech.2021.113794]

5. Zhang X, Wang Y, Ji J, Si D, Bao X, Yu Z, Zhu Y, Zhao L, Li W, Liu J..  (2022)  Discovery of 1,6-Naphthyridin-2(1H)-one Derivatives as Novel, Potent, and Selective FGFR4 Inhibitors for the Treatment of Hepatocellular Carcinoma.,  65  (11.0): [PMID:35635004] [10.1021/acs.jmedchem.1c01977]

6. Xie W, Yang S, Liang L, Wang M, Zuo W, Lei Y, Zhang Y, Tang W, Lu T, Chen Y, Jiang Y..  (2022)  Discovery of 2-Amino-7-sulfonyl-7H-pyrrolo[2,3-d]pyrimidine Derivatives as Potent Reversible FGFR Inhibitors with Gatekeeper Mutation Tolerance: Design, Synthesis, and Biological Evaluation.,  65  (24.0): [PMID:36480917] [10.1021/acs.jmedchem.2c01420]

Source

Source(3):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names