1217486-61-7

Basic information

• Product Name: (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide
• Synonyms: (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide;BYL-719;BYL-719 /BYL719;BLV-719;(S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-Methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxaMide;Alpelisib;1,2-Pyrrolidinedicarboxamide, N1-[4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-, (2S)-;Alpelisib (BYL719)
• CAS NO: 1217486-61-7
• Molecular Formula: C₁₉H₂₂F₃N₅O₂S
• Molecular Weight: 441.4704896
• Product Categories: PI3K/Akt/mTOR;Inhibitors;Akt;mTOR;PI3K
• Mol File: 1217486-61-7.mol

Chemical Properties

• Appearance: /
• Density: 1.391
• Solubility: ≥22.07 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
• PKA: 6.29±0.70(Predicted)
• CAS DataBase Reference: (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide(1217486-61-7)
• EPA Substance Registry System: (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide(1217486-61-7)

Safety Data

• Hazardous Substances Data: 1217486-61-7(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
BYL719 is used as an antineoplastic agent for the treatment of advanced or metastatic breast cancer. It works by inhibiting the PI3Kα isoform, which is often mutated or overexpressed in various cancers, leading to uncontrolled cell proliferation and tumor growth. By targeting this pathway, BYL719 can potentially halt or slow down the progression of cancer, offering a new treatment option for patients with breast cancer.
Used in Leukemia Treatment:
In addition to breast cancer, BYL719 has shown promise in the treatment of THP-1 acute myeloid leukemia (AML). As a PI3Kα and mTOR inhibitor, it can help reduce the tumor burden in AML patients by disrupting the signaling pathways that support the growth and survival of leukemia cells.
Used in Drug Development for Proliferative Diseases:
BYL719's dual inhibition of PI3Kα and mTOR makes it a valuable compound in the development of new therapies for a range of proliferative diseases. Its ability to target key signaling pathways involved in cell growth and proliferation positions it as a potential treatment option for various types of cancer and other diseases characterized by abnormal cell proliferation.
Used in Preclinical and Clinical Research:
BYL719 is also utilized in preclinical and clinical research settings to better understand the role of the PI3K/AKT/mTOR pathway in cancer development and progression. Its use in these studies can provide valuable insights into the mechanisms of action, potential side effects, and optimal dosing strategies for this class of inhibitors, ultimately contributing to the development of more effective and targeted cancer treatments.

references

1. furet p, guagnano v, fairhurst ra et al. discovery of nvp-byl719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. bioorg med chem lett 2013; 23: 3741-3748. 2. azab f, vali s, abraham j et al. pi3kca plays a major role in multiple myeloma and its inhibition with byl719 decreases proliferation, synergizes with other therapies and overcomes stroma-induced resistance. br j haematol 2014; 165: 89-101. 3. juric d, argiles g, burris h et al. phase i study of byl719, an alpha-specific pi3k inhibitor, in patients with pik3ca mutant advanced solid tumors: preliminary efficacy and safety in patients with pik3ca mutant er-positive (er+) metastatic breast cancer (mbc). cancer res 2012; 72: p6-10.

Upstream product

• 108-47-4 2,4-lutidine 
• 59576-26-0 2-acetyl-4-methylpyridine 
• 1396893-41-6 C₂₀H₁₈F₃N₃O₂S 
• 7531-52-4 L-prolinamide 
• 1378865-93-0 4-methyl-2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridine 
• 1396893-39-2 1-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridyl]-2-propanone 
• 1396893-42-7 4-methyl-2-(2,2,2-trifluoro-1-methyl-1-trimethylsilanyloxy-ethyl)pyridine 
• 1396893-43-8 1,1,1-trifluoro-2-(4-methylpyridin-2-yl)propan-2-ol 
• 1396893-44-9 1,1,1-trifluoro-2-(4-methylpyridin-2-yl)propan-2-yl methanesulfonate 
• 1396893-45-0 C₁₂H₁₇NO₂ 
• 1396893-46-1 C₁₀H₁₂NO₂^(1-)*Na⁽¹⁺⁾ 
• 889940-13-0 3,3,3-trifluoro-2,2-dimethylpropanoic acid 
• 1163707-53-6 3,3,3-trifluoro-2,2-dimethylpropanoyl chloride 
• 1357476-64-2 2-(1,1,1-trifluoro-2-methylpropan-2-yl)-4H-pyran-4-one 

Relevant articles and documents

Preparation method of alpelisib

The invention provides a preparation method of alpelisib. 2-pyrrole methyl formate and N, N-carbonyldiimidazole which are used as raw materials are subjected to an amidation reaction, a suzuki reaction and an aminolysis reaction to obtain the compound apenelisib shown in the formula I. The method is mild in reaction condition, simple and convenient in treatment, environment-friendly, low in cost and suitable for industrial mass production.

Producing Method for 4,4′-oxydianiline from nitrochlorobenzene and nitrophenolate salt

The present invention relates to a method for manufacturing 4,4′-oxydianiline, including: a first step of obtaining a reactant including dinitrodiphenyl ether by mixing and inducing a reaction of nitrochlorobenzene and a nitrophenolate salt under a hydrotalcite catalyst in which an organic acid is intercalated; a second step of obtaining a reaction product by hydrogenating the reactant including dinitrodiphenyl ether. The present invention proposes a novel manufacturing method related to mass production of 4,4′-oxydianiline as a raw material for polyimides, a high yield of dinitrodiphenyl ether as a raw material for 4,4′-oxydianiline, and the like.

Preparation method of alpelisib

The invention discloses a preparation method of alpelisib (alpelisib). The preparation method comprises sequentially subjecting S-prolinamide as a raw material to acylation reaction, thiourea reaction, bromination cyclization and other basic unit reactions to obtain alpelisib. The preparation method has the advantages of easily available raw materials, simple process, economical property, environmental protection and suitability for industrial production.

Novel synthesis method of PI3K inhibitor Alpelisib

The invention relates to a novel synthesis method of a PI3K inhibitor Alpelisib. According to the synthesis method disclosed by the invention, the target molecule can be synthesized through four stepsof reactions including one-step substitution reaction of starting raw materials, amino protection group removal and two times of halogenation reaction, the total yield is high, the cost is low, and the HPLC purity of the product reaches 99.5% or above.

Preparation process of Alpelisib

The invention relates to a preparation process of Alpelisib. The preparation process has the advantages of few reaction steps, simple process, mild reaction conditions, no extreme low-temperature reaction, simple purifying and low overall reaction difficulty, and is suitable for large-scale production.

A PHARMACEUTICAL COMBINATION COMPRISING THE PI3K INHIBITOR ALPELISIB AND THE CDK4/6 INHIBITOR RIBOCICLIB, AND THE USE THEREOF IN THE TREATMENT/PREVENTION OF CANCER

The present disclosure pertains to a pharmaceutical combination comprising (a) an alpha- isoform specific PI3K inhibitor, (b) a cyclin dependent kinase 4/6 (CDK4/6) inhibitor, and (c) an antimetabolite antineoplastic agent; combined preparations and pharmaceutical compositions thereof; the uses of such a combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

COMBINATION THERAPY

The present disclosure pertains to a pharmaceutical combination comprising (a) alpha- isoform specific PI3K inhibitor and (b) an AKT inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject in need thereof comprising administering a therapeutically effective amount of such combination. 43

PHARMACEUTICAL COMBINATION COMPRISING THE PI3K INHIBITOR ALPELISIB AND THE B-RAF INHIBITOR DABRAFENIB; THE USE OF SUCH COMBINATION IN THE TREATMENT OR PREVENTION OF CANCER

The present disclosure pertains to a pharmaceutical combination comprising (a) alpha- isoform specific PI3K inhibitor and (b) a B-RAF inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

COMBINATION THERAPY

The present invention relates to a pharmaceutical combination comprising an alpha-isoform specific phosphatidylinositol 3-kinase inhibitor compound, such as (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide), or pharmaceutically acceptable salt thereof, and an IGF1R inhibitor (e.g., the IGF1R inhibitor ANTIBODY A, or a variant or derivative thereof), a pharmaceutical composition comprising such combination, methods for treating cancer comprising administration of therapeutically effective amounts of such inhibitors to a subject in need thereof, and uses of such combination for the treatment of cancer.

Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation

Phosphatidylinositol-3-kinase α (PI3Kα) is a therapeutic target of high interest in anticancer drug research. On the basis of a binding model rationalizing the high selectivity and potency of a particular series of 2-aminothiazole compounds in inhibiting PI3Kα, a medicinal chemistry program has led to the discovery of the clinical candidate NVP-BYL719.