TIRABRUTINIB

ID: ALA4071161

Cas Number: 1351636-18-4

PubChem CID: 54755438

Product Number: T614478, Order Now?

Max Phase: Approved

First Approval: 2020

Molecular Formula: C25H22N6O3

Molecular Weight: 454.49

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Gs-4059 | Ono-4059 | Tirabrutinib | GS-4059 | ONO-4059 | ONO-4059(FREE BASE) | Tirabrutinib|ONO-4059|1351636-18-4|GS-4059|ONO-4059(Free base)|Tirabrutinib [INN]|Tirabrutinib free base|LXG44NDL2T|Btk Kinase inhibitor|UNII-LXG44NDL2T|ONO4059|(R)-6-amino-9-(1-(but-2-ynoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one|1351636-18-4 (free base)|Velexbru|(R)-6-amino-9-(1-(but-2-ynoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one|6-amino-9-[(3R)-1-but-2-ynoylpyrrolidin-3-yl]-Show More⌵

Synonyms from Alternative Forms(3): GS-4059 hydrochloride | ONO-4059 hydrochloride | Tirabrutinib hydrochloride

Trade Names(1): Velexbru

Canonical SMILES:  CC#CC(=O)N1CC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1

Standard InChI:  InChI=1S/C25H22N6O3/c1-2-6-21(32)29-14-13-18(15-29)31-24-22(23(26)27-16-28-24)30(25(31)33)17-9-11-20(12-10-17)34-19-7-4-3-5-8-19/h3-5,7-12,16,18H,13-15H2,1H3,(H2,26,27,28)/t18-/m1/s1

Standard InChI Key:  SEJLPXCPMNSRAM-GOSISDBHSA-N

Molfile:  

     RDKit          2D

 34 38  0  0  0  0  0  0  0  0999 V2000
   -4.9041    0.3800    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4659   -0.2241    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2236   -1.0127    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4195   -1.1972    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8577   -0.5931    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1000    0.1956    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4918   -0.1734    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7341    0.6152    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5382    0.7997    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6876   -0.3579    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1258    0.2463    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3681    1.0349    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1722    1.2194    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3220    0.5015    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3939    1.3233    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.9978    0.0283    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7455    0.3769    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8174    1.1988    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5049    0.0545    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0462    0.6772    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6213    1.3843    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3369    0.0050    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0683   -0.7750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7565   -0.7607    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4683   -1.4966    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0434   -2.2038    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.7814   -2.1894    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1814   -1.4679    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8680    0.6053    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3412    1.2810    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2167   -0.1425    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.8144    1.9568    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2876    2.6326    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2932   -1.5109    0.0000 N   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
  7  8  2  0
  8  9  1  0
  6  9  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
  7 10  1  0
  8 13  1  0
 14 15  2  0
 17 16  1  6
 17 18  1  0
 14 16  1  0
 19 20  1  0
 20 21  1  0
 17 19  1  0
 18 21  1  0
 22 23  1  0
 23 24  2  0
 14 22  1  0
 16 24  1  0
 11 22  1  0
 25 26  2  0
 26 27  1  0
 27 28  2  0
 23 25  1  0
 24 28  1  0
 20 29  1  0
 29 30  1  0
 29 31  2  0
 30 32  3  0
 32 33  1  0
 25 34  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4071161

   tirabrutinib

2. Alternative Forms:

   

   ALA4071161

   TIRABRUTINIB HYDROCHLORIDE

Molecule Features

Natural Product: No

Oral: Yes

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: 454.49

Molecular Weight (Monoisotopic): 454.1753

AlogP: 2.75

#Rotatable Bonds: 4

Polar Surface Area: 108.27

Molecular Species: NEUTRAL

HBA: 8

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 3.33

CX LogP: 3.27

CX LogD: 3.27

Aromatic Rings: 4

Heavy Atoms: 34

QED Weighted: 0.48

Np Likeness Score: -0.69

References

1. Unpublished dataset, 

2.  (2015)  Purinone derivative hydrochloride, 

3. Crawford JJ, Johnson AR, Misner DL, Belmont LD, Castanedo G, Choy R, Coraggio M, Dong L, Eigenbrot C, Erickson R, Ghilardi N, Hau J, Katewa A, Kohli PB, Lee W, Lubach JW, McKenzie BS, Ortwine DF, Schutt L, Tay S, Wei B, Reif K, Liu L, Wong H, Young WB..  (2018)  Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton's Tyrosine Kinase Inhibitor in Early Clinical Development.,  61  (6): [PMID:29457982] [10.1021/acs.jmedchem.7b01712]

4. Angst D, Gessier F, Janser P, Vulpetti A, Wälchli R, Beerli C, Littlewood-Evans A, Dawson J, Nuesslein-Hildesheim B, Wieczorek G, Gutmann S, Scheufler C, Hinniger A, Zimmerlin A, Funhoff EG, Pulz R, Cenni B..  (2020)  Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.,  63  (10): [PMID:32083858] [10.1021/acs.jmedchem.9b01916]

5. Foster H,Wilson C,Philippou H,Foster R.  (2020)  Progress toward a Glycoprotein VI Modulator for the Treatment of Thrombosis.,  63  (21): [PMID:32463237] [10.1021/acs.jmedchem.0c00262]

6. Ran F, Liu Y, Wang C, Xu Z, Zhang Y, Liu Y, Zhao G, Ling Y..  (2022)  Review of the development of BTK inhibitors in overcoming the clinical limitations of ibrutinib.,  229  [PMID:34839996] [10.1016/j.ejmech.2021.114009]

7. Guo Y, Hu N, Liu Y, Zhang W, Yu D, Shi G, Zhang B, Yin L, Wei M, Yuan X, Luo L, Wang F, Song X, Xin L, Wei Q, Li Y, Guo Y, Chen S, Zhang T, Zhang S, Zhou X, Zhang C, Su D, Liu J, Cheng Z, Zhang J, Xing H, Sun H, Li X, Zhao Y, He M, Wu Y, Guo Y, Sun X, Tian A, Zhou C, Young S, Liu X, Wang L, Wang Z..  (2023)  Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase for B-Cell Malignancies and Autoimmune Diseases.,  66  (6): [PMID:36912866] [10.1021/acs.jmedchem.2c01938]

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

Source

Source(4):

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