CAS 1223405-08-0

Chemistry

Chemistry

Also known as: 1223405-08-0, Loxo-101 sulfate, Arry-470 sulfate, Loxo-101 (sulfate), (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide sulfate, Rdf76r62id

Molecular Formula

C₂₁H₂₄F₂N₆O₆S

Molecular Weight

526.5 g/mol

InChI Key

PXHANKVTFWSDSG-QLOBERJESA-N

FDA UNII

RDF76R62ID

Larotrectinib Sulfate is the sulfate salt form of larotrectinib, an orally available, tropomyosin receptor kinase (Trk) inhibitor, with potential antineoplastic activity. Upon administration, larotrectinib binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation, which results in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress Trk. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.

1 2D Structure

CAS 1223405-08-0

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

(3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide;sulfuric acid

2.1.2 InChI

InChI=1S/C21H22F2N6O2.H2O4S/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27;1-5(2,3)4/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31);(H2,1,2,3,4)/t14-,18+;/m0./s1

2.1.3 InChI Key

PXHANKVTFWSDSG-QLOBERJESA-N

2.1.4 Canonical SMILES

C1CC(N(C1)C2=NC3=C(C=NN3C=C2)NC(=O)N4CCC(C4)O)C5=C(C=CC(=C5)F)F.OS(=O)(=O)O

2.1.5 Isomeric SMILES

C1C[C@@H](N(C1)C2=NC3=C(C=NN3C=C2)NC(=O)N4CC[C@@H](C4)O)C5=C(C=CC(=C5)F)F.OS(=O)(=O)O

2.2 Other Identifiers

2.2.1 UNII

RDF76R62ID

2.3 Synonyms

2.3.1 MeSH Synonyms

1. (3s)-n-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo(1,5-a)pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide

2. Arry-470

3. Arry470

4. Bay-2757556

5. Bay2757556

6. Larotrectinib

7. Loxo-101

8. Loxo101

9. N-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo(1,5-a)pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide

10. Vitrakvi

2.3.2 Depositor-Supplied Synonyms

1. 1223405-08-0

2. Loxo-101 Sulfate

3. Arry-470 Sulfate

4. Loxo-101 (sulfate)

5. (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide Sulfate

6. Rdf76r62id

7. Larotrectinib Sulfate [usan]

8. Vitrakvi

9. (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide;sulfuric Acid

10. 1-pyrrolidinecarboxamide, N-(5-((2r)-2-(2,5-difluorophenyl)-1-pyrrolidinyl)pyrazolo(1,5-a)pyrimidin-3-yl)-3-hydroxy-, (3s)-, Sulfate (1:1)

11. Vitrakvi (tn)

12. 1-pyrrolidinecarboxamide, N-[5-[(2r)-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-, (3s)-, Sulfate (1:1)

13. Larotrectinib (loxo-101) Sulfate

14. Larotrectinib Sulphate

15. Loxo-101(sulfate)

16. Arry-470 (sulfate)

17. Unii-rdf76r62id

18. Schembl2239598

19. Chembl3989939

20. Ex-a1981a

21. Dtxsid401026485

22. Hms3886n19

23. Larotrectinib Sulfate (jan/usan)

24. Larotrectinib Sulfate [mi]

25. Larotrectinib Sulfate [jan]

26. Amy12423

27. Larotrectinib (loxo-101 Sulfate)

28. Hy-12866a

29. Mfcd29472286

30. S7960

31. Larotrectinib Sulfate [who-dd]

32. Ccg-269890

33. Cs-5314

34. Ac-30671

35. Bl161518

36. Larotrectinib Sulfate [orange Book]

37. D11138

38. (3s)-n-(5-((2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo(1,5-a)pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide Sulfate (1:1)

39. (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide Hydrogen Sulfate

2.4 Create Date

2012-11-30

3 Chemical and Physical Properties

Molecular Formula	C₂₁H₂₄F₂N₆O₆S
Molecular Weight	526.5 g/mol
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	3
Exact Mass	526.14461000 g/mol
Monoisotopic Mass	526.14461000 g/mol
Topological Polar Surface Area	169 Å²
Heavy Atom Count	36
Formal Charge	0
Complexity	741
Isotope Atom Count	0
Defined Atom Stereocenter Count	2
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	2

4 Drug and Medication Information

4.1 Drug Indication

Vitrakvi as monotherapy is indicated for the treatment of adult and paediatric patients with solid tumours that display a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion,

- who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and

- who have no satisfactory treatment options.

5 Pharmacology and Biochemistry

5.1 ATC Code

L01XE53