CAS 1421373-65-0 manufacturers and suppliers on PharmaCompass

CAS 1421373-65-0

Virtual Booth

Contact Supplier

Fishfa Biogenics: Renowned Manufacturer, & Exporter of Tacrolimus & Mupirocin API.

CHEMISTRY

Discover Molecule Insights

BUILDING BLOCK

2 Suppliers, 1 End Use APIs, 39 Related Intermediates

2 Suppliers
1 End Use APIs
39 Related Intermediates

MARKET PLACE

1 APIs

1 APIs

Chemistry

Click the arrow to open the dropdown

Click the button for full data set

Also known as: 1421373-65-0, Azd-9291, Mereletinib, Azd9291, Azd 9291, Osimertinib [usan]

Molecular Formula

C₂₈H₃₃N₇O₂

Molecular Weight

499.6 g/mol

InChI Key

DUYJMQONPNNFPI-UHFFFAOYSA-N

FDA UNII

3C06JJ0Z2O

Osimertinib is a third-generation, orally available, irreversible, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, osimertinib covalently binds to and inhibits the activity of numerous mutant forms of EGFR, including the secondarily-acquired resistance mutation T790M, L858R, and exon 19 deletions, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.

Osimertinib is a Kinase Inhibitor. The mechanism of action of osimertinib is as a Kinase Inhibitor, and Cytochrome P450 3A Inhibitor, and Cytochrome P450 3A4 Inducer, and Cytochrome P450 1A2 Inducer, and Breast Cancer Resistance Protein Inhibitor.

1 2D Structure

CAS 1421373-65-0

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide

2.1.2 InChI

InChI=1S/C28H33N7O2/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32)

2.1.3 InChI Key

DUYJMQONPNNFPI-UHFFFAOYSA-N

2.1.4 Canonical SMILES

CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC

2.2 Other Identifiers

2.2.1 UNII

3C06JJ0Z2O

2.3 Synonyms

2.3.1 MeSH Synonyms

1. Azd-9291

2. Azd-9291 Mesylate

3. Azd9291

4. Azd9291 Mesylate

5. Mereletinib

6. Mereletinib Mesilate

7. Mereletinib Mesylate

8. N-(2-((2-(dimethylamino)ethyl)methylamino)-4-methoxy-5-((4-(1-methyl-1h-indol-3-yl)-2-pyrimidinyl)amino)phenyl)-2-propenamide

9. N-(2-((2-(dimethylamino)ethyl)methylamino)-4-methoxy-5-((4-(1-methyl-1h-indol-3-yl)-2-pyrimidinyl)amino)phenyl)-2-propenamide Methanesulfonate (1:1)

10. Osimertinib Mesilate

11. Osimertinib Mesylate

12. Tagrisso

2.3.2 Depositor-Supplied Synonyms

1. 1421373-65-0

2. Azd-9291

3. Mereletinib

4. Azd9291

5. Azd 9291

6. Osimertinib [usan]

7. Unii-3c06jj0z2o

8. N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide

9. 3c06jj0z2o

10. Azd-9291 Free Base

11. N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1h-indol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide

12. N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1h-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide

13. 2-propenamide, N-(2-((2-(dimethylamino)ethyl)methylamino)-4-methoxy-5-((4-(1-methyl-1h-indol-3-yl)-2-pyrimidinyl)amino)phenyl)-

14. N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide

15. N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1h-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-propenamide

16. Mereletinib [inn]

17. Osimertinibum

18. N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1h-indol-3-yl)pyrimidin-2-yl]amino}phenyl)acrylamide

19. Osimertinib [mi]

20. Osimertinib [inn]

21. Osimertinib (azd9291)

22. Osimertinib; Azd 9291

23. Osimertinib; Azd-9291

24. Mereletinib (obsolete Inn)

25. Osimertinib [who-dd]

26. Gtpl7719

27. Chembl3353410

28. Schembl14660911

29. Chebi:90943

30. Amy9161

31. Ex-a314

32. Mereletinibazd-9291,osimertinib

33. Dtxsid501025961

34. Hms3653e10

35. Hms3672m05

36. Bcp08626

37. Bdbm50029668

38. Mfcd27988062

39. Nsc779217

40. Nsc781254

41. Nsc800812

42. S7297

43. Zinc98023177

44. Akos025290756

45. Ccg-264683

46. Cs-2018

47. Db09330

48. Nsc-779217

49. Nsc-781254

50. Nsc-800812

51. Sb22952

52. Ncgc00378622-03

53. Ncgc00378622-04

54. Ncgc00378622-10

55. Ac-29019

56. As-16943

57. Hy-15772

58. 4714b

59. Sw219863-1

60. A854509

61. Q21506464

62. N(2{[2(dimethylamino)ethyl](methyl)amino}4methoxy5{[4(1methyl1hindol3yl)pyrimidin2yl]amino}phenyl)prop2enamide;osimertinib

63. N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-(4-(1-methyl-1h-indol-3-yl)pyrimidin-2-ylamino)phenyl)acrylamide

64. N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide

2.4 Create Date

2013-06-10

3 Chemical and Physical Properties

Molecular Formula	C₂₈H₃₃N₇O₂
Molecular Weight	499.6 g/mol
XLogP3	3.7
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	10
Exact Mass	499.26957332 g/mol
Monoisotopic Mass	499.26957332 g/mol
Topological Polar Surface Area	87.6 Å²
Heavy Atom Count	37
Formal Charge	0
Complexity	752
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Information

1 of 1
Drug Name	TAGRISSO
Active Ingredient	OSIMERTINIB MESYLATE
Company	ASTRAZENECA PHARMS (Application Number: N208065. Patents: 8946235, 9732058)

4.2 Drug Indication

Osimertinib is indicated for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA- approved test, who have progressed on or after EGFR-TKI therapy.

FDA Label

TAGRISSO as monotherapy is indicated for:

-the adjuvant treatment after complete tumour resection in adult patients with stage IB-IIIA non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations

- the first-line treatment of adult patients NSCLC with activating EGFR mutations.

- the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC.

TAGRISSO as monotherapy is indicated for:

- the adjuvant treatment after complete tumour resection in adult patients with stage IB-IIIA non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

- the first-line treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR mutations.

- the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC.

5 Pharmacology and Biochemistry

5.1 Pharmacology

A pharmacokinetic/pharmacodynamic analysis suggested a concentration-dependent QTc interval prolongation of 14 msec (upper bound of two-sided 90% CI: 16 msec) at a dose of osimertinib 80 mg.

5.2 MeSH Pharmacological Classification

Antineoplastic Agents

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

Protein Kinase Inhibitors

Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)

5.3 FDA Pharmacological Classification

5.3.1 Active Moiety

OSIMERTINIB

5.3.2 FDA UNII

3C06JJ0Z2O

5.3.3 Pharmacological Classes

Cytochrome P450 1A2 Inducers [MoA]; Cytochrome P450 3A Inhibitors [MoA]; Cytochrome P450 3A4 Inducers [MoA]; Kinase Inhibitor [EPC]; Kinase Inhibitors [MoA]; Breast Cancer Resistance Protein Inhibitors [MoA]

5.4 ATC Code

L01XE

L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01E - Protein kinase inhibitors

L01EB - Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors

L01EB04 - Osimertinib

5.5 Absorption, Distribution and Excretion

Absorption

The median time to Cmax was found to be 6 hours.

Route of Elimination

Osimertinib is primarily eliminated through excretion in the feces (68%), to a lesser extent through urine (14%), while only 2% is excreted unchanged.

Volume of Distribution

The mean volume of distribution at steady state is 986 L.

Clearance

Oral clearance is 14.2 L/hr.

5.6 Metabolism/Metabolites

Osimertinib is metabolized to at least two pharmacologically active metabolites, AZ7550 and AZ5104, that circulate at approximately 10% of the concentration of the parent compound. Biochemical assays have shown that AZ7550 has similar potency and efficacy to osimertinib, while AZ5104 is more potent against mutant and wild-type EGFR. The main metabolic pathways are oxidation (predominantly by CYP3A) and dealkylation.

5.7 Biological Half-Life

The population estimated mean half-life is 48 hours.

5.8 Mechanism of Action

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that binds to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) that predominate in non-small cell lung cancer (NSCLC) tumours following treatment with first-line EGFR-TKIs. As a third-generation tyrosine kinase inhibitor, osimertinib is specific for the gate-keeper T790M mutation which increases ATP binding activity to EGFR and results in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.

BUILDING BLOCK

Upload your portfolio for free, ask us