Cas 557795-19-4,Sunitinib | lookchem (2025)

Uses

Used in Anticancer Applications:
Sunitinib is used as an antineoplastic agent for inhibiting the growth of tumor cells expressing dysregulated target RTKs, such as PDGFR, VEGFR, and KIT. It modulates several oncological signaling pathways, including VEGFR2 (Flk-1) and PDGFRβ, exerting inhibitory effects on tumor growth and progression. Additionally, it demonstrates synergistic anticancer effects when combined with conventional chemotherapeutic drugs, enhancing chemo-sensitivity and efficacy in resistant cases.
Used in Pharmaceutical Industry:
Sunitinib is used as a multi-targeted RTK inhibitor for the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for sunitinib delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.

Originator

Sugen (US)

Clinical Use

Tyrosine kinase inhibitor:Treatment of metastatic renal cell carcinoma (MRCC), gastrointestinal stromal tumours (GIST) and pancreatic neuroendocrine tumours (pNET)

Drug interactions

Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine (increased risk of agranulocytosis). Antivirals: avoid concomitant use with boceprevir. Avoid concomitant use with other inhibitors or inducers of CYP3A4. Dose alterations may be required.

Metabolism

Metabolised mainly via the cytochrome P450 isoenzyme CYP3A4 to its primary active metabolite, which itself is then further metabolised via CYP3A4.Elimination is primarily via faeces. In a human mass balance study of [14C]sunitinib, 61% of the dose was eliminated in faeces and 16% by the renal route.

references

[1]hui ep1, lui vw, wong cs, ma bb, lau cp, cheung cs, ho k, cheng sh, ng mh, chan at. preclinical evaluation of sunitinib as single agent or in combination with chemotherapy in nasopharyngeal carcinoma. invest new drugs. 2011 dec;29(6):1123-31.

Check Digit Verification of cas no

The CAS Registry Mumber 557795-19-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,5,7,7,9 and 5 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 557795-19:
(8*5)+(7*5)+(6*7)+(5*7)+(4*9)+(3*5)+(2*1)+(1*9)=214
214 % 10 = 4
So 557795-19-4 is a valid CAS Registry Number.

AMP-ACTIVATED PROTEIN KINASE INHIBITORS AND METHODS OF MAKING AND USING THE SAME

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Page/Page column 64-65; 66, (2021/01/23)

The present disclosure relates to compounds of Formula (I): (I); stereoisomers thereof, prodrugs thereof, and pharmaceutically acceptable salts thereof. The present disclosure also relates to uses of the compounds, e.g., to inhibit AMP-Activated protein kinase (AMPK) and treat cancer in a subject.

Substituted oxindol-3-ylidenes as AMP-activated protein kinase (AMPK) inhibitors

Backos, Donald S.,Casalvieri, Kimberly A.,Jordan, Craig T.,Matheson, Christopher J.,Minhajuddin, Mohammed,Reigan, Philip

, (2020/04/22)

AMP-activated protein kinase (AMPK) is a central metabolic regulator that promotes cancer growth and survival under hypoxia and plays a role in the maintenance of cancer stem cells. A major challenge to interrogating the potential of targeting AMPK in cancer is the lack of potent and selective small molecule inhibitors. Compound C has been widely used as an AMPK inhibitor, but it lacks potency and has a poor selectivity profile. The multi-kinase inhibitor, sunitinib, has demonstrated potent nanomolar inhibition of AMPK activity and has scope for modification. Here, we have designed and synthesized several series of oxindoles to determine the structural requirements for AMPK inhibition and to improve selectivity. We identified two potent, novel oxindole-based AMPK inhibitors that were designed to interact with the DFG motif in the ATP-binding site of AMPK, this key feature evades interaction with the common recptor tyrosine kinase targets of sunitinib. Cellular engagement of AMPK by these oxindoles was confirmed by the inhibition of phosphorylation of acetyl-CoA carboxylase (ACC), a known substrate of AMPK, in myeloid leukemia cells. Interestingly, although AMPK is highly expressed and activated in K562 cells these oxindole-based AMPK inhibitors did not impact cell viability or result in significant cytotoxicity. Our studies serve as a platform for the further development of oxindole-based AMPK inhibitors with therapeutic potential.

A high-purity malic acid lin's preparation method

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Paragraph 0042; 0043, (2019/04/04)

The invention relates to a high-purity malic acid lin's preparation method, the method comprises the following steps: (1) the formula II compound as a starting material, the use of 1 - ethyl - (3 - dimethyl amino propyl) carbonylamino-carbodiimide hydrochloride with 1 - hydroxy benzotriazole as the condensing agent, under certain temperature and N, N diethylethylenediamine reaction to obtain compound III; (2) in the step (1) the reaction solution, between the step (1) the resulting reactant with 5 - fluoro indole - 2 - one reaction at certain temperature, to obtain compound IV; (3) in the step (2) of the reaction solution, so that the step (1) the resulting reactant with L - malic acid reaction at certain temperature, to obtain compound I; providing at least to a certain extent one of the solve the above technical problems or at least provide a useful commercial choice. The reaction route is operating time is short, simple operation, reaction system is stable, higher product yield, purity of the product is relatively high, it is suitable for industrial production.

Metalloporphyrin-Catalyzed Oxidation of Sunitinib and Pazopanib, Two Anticancer Tyrosine Kinase Inhibitors: Evidence for New Potentially Toxic Metabolites

Paludetto, Marie-No?lle,Bijani, Christian,Puisset, Florent,Bernardes-Génisson, Vania,Arellano, Cécile,Robert, Anne

, p. 7849 - 7860 (2018/09/06)

Oxidation of two tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib, using a chemical catalytic system able to mimic the cytochrome P450 type oxidation, allowed us to prepare putative reactive/toxic metabolites of these anticancer drugs. Among these metabolites, aromatic aldehyde derivatives were unambiguously characterized. Such biomimetic oxidation of TKI-type drugs was essential to facilitate the identification of low amounts of aldehydes generated from these TKIs when incubated with human liver microsomes (HLM), which are classical models of human hepatic metabolism. These TKI derivative aldehydes quickly react in vitro with amines. A similar reaction is expected to occur in vivo and may be at the origin of the potentially severe hepatotoxicity of these TKIs.

High-purity L-sunitinib malate preparation method

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Paragraph 0048; 0049, (2017/08/28)

The present invention discloses a high-purity L-sunitinib malate preparation method, which comprises the following reaction route defined in the specification, wherein the step a comprises that a B5 compound and 5-fluoroindol-2-one are subjected to an Aldol condensation reaction to obtain a sunitinib free base (B6 compound), the step b comprises that the B6 compound and L-malic acid are subjected to a salt forming reaction to obtain the L-sunitinib malate, and the step a and the step b are performed in a dark place. According to the present invention, the HPLC purity of the prepared L-sunitinib malate can achieve more than 99.8%, the single impurity content can be controlled at less than 0.1%, and the quality difficulty of the application of the L-sunitinib malate in the preparation is effectively solved.

Unique physicochemical and catalytic properties dictated by the B3NO2 ring system

Noda, Hidetoshi,Furutachi, Makoto,Asada, Yasuko,Shibasaki, Masakatsu,Kumagai, Naoya

, p. 571 - 577 (2017/06/01)

The expansion of molecular diversity beyond what nature can produce is a fundamental objective in chemical sciences. Despite the rich chemistry of boron-containing heterocycles, the 1,3-dioxa-5-aza-2,4,6-triborinane (DATB) ring system, which is characterized by a six-membered B3NO2 core, remains elusive. Here, we report the synthesis of m-terphenyl-templated DATB derivatives, displaying high stability and peculiar Lewis acidity arising from the three suitably arranged boron atoms. We identify a particular utility for DATB in the dehydrative amidation of carboxylic acids and amines, a reaction of high academic and industrial importance. The three boron sites are proposed to engage in substrate assembly, lowering the entropic cost of the transition state, in contrast with the operative mechanism of previously reported catalysts and amide coupling reagents. The distinct mechanistic pathway dictated by the DATB core will advance not only such amidations, but also other reactions driven by multisite activation.

A process for the preparation of nun

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Paragraph 0129-0138, (2020/02/07)

The invention relates to a method for preparing sunitinib. The method comprises the steps of dissolving 5-fluoro-1,3-indoline-2-ketone and N-(2-diethylin ethyl)-2,4-dimethyl-5-formyl group-1H-pyrrole-3-formamide into methylbenzene, then carrying out backflow reaction for 2.5-3.5 hours with piperidine as a catalyst, cooling to room temperature, carrying out suction filtering, and washing and drying filter cakes obtained by suction filtration through petroleum ether, so as to obtain the sunitinib, wherein the N-(2-diethylin ethyl)-2,4-dimethyl-5-formyl group-1H-pyrrole-3-formamide is prepared through hot melting and decarboxylation of 3,5-dimethyl-1H-pyrrole-4-carbethoxy-2-carboxylic acid, Vilsmeier-Haack formylation, hydrolysis reaction and amidation. According to the method, an intermediate of the sunitinib is prepared and synthesized through a solvent-free method, so that the overall yield of the sunitinib is greatly increased; in addition, the technology for elementary reaction is optimized; furthermore, the raw materials are easy to obtain, and by optimizing all reaction steps in the synthetic process, the elementary reaction yield of each step is increased, the total yield of the sunitinib is increased, and thus the synthetic cost of the sunitinib is lowered.

An improved synthesis of sunitinib malate via a solvent-free decarboxylation process

Meng, Ge,Liu, Chunyan,Qin, Shidong,Dong, Mengshu,Wei, Xiaomi,Zheng, Meilin,Qin, Liwen,Wang, Huihui,He, Xiaoshuang,Zhang, Zhiguo

, p. 8941 - 8954 (2015/10/28)

To search for an economical and convenient synthesis of sunitinib and its malate salt, optimization of a scalable synthetic route was explored by designing a standard experimental protocol on laboratory scale using commercially available materials including acetyl ethyl acetate, 4-fluoroaniline, and N 1,N 1-diethylethane-1,2-diamine. The optimal conditions were established based on investigating the main reaction steps, including cyclization, hydrolysis, decarboxylation, formylation, and condensation, giving optimized yields for each step of 94.4, 97.6, 98.5, 97.1, 91.0, 86.3, 85.5, 88.2, 99.1, 97.3, and 58.7 %, respectively. The synthesis process of 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid as the important intermediate was significantly improved by using solvent-free decarboxylation instead of the traditional process in a high-boiling-point solvent. The subsequent formylation was conducted directly using the dichloromethane solution of the crude product from decarboxylation, leading to an almost quantitative combined yield of these two steps. The overall yields of sunitinib and its salt using the optimal synthesis process were 67.3 and 40.0 % based on acetyl ethyl acetate. The obtained data could be used as reference for future industrialization, especially for avoiding expensive solvents and reducing reaction time.

PROCESS FOR THE PERPARATION OF SUNITINIB AND ITS ACID ADDITION SALTS THEREOF

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Paragraph 0113, (2015/02/18)

The present invention relates to an improved process for the preparation of Sunitinb. The process involves the activation of 5-((Z)-(5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4-dimethyl-1H-pyrrole-3carboxylic acid to corresponding suitable carboxylic acid activating group. The present invention also relates to novel acid addition salts of Sunitinb and preparation thereof.

Synthesis of sunitinib-metastin conjugate, a novel esterase-sensitive prodrug system based on lactonization reaction

Takahashi, Yuki,Shoji, Sunao,Morishige, Takuya,Katsumata, Aya,Tsurifune, Fumihiro,Tsutsumi, Mitsuhiro,Honda, Yoshiharu,Hasuda, Tomoyo,Hitotsuyanagi, Yukio,Terachi, Toshiro,Uchida, Toyoaki,Takeya, Koichi

, p. 1860 - 1876 (2014/08/18)

We describe a strategy for preparing sunitinib-metastin conjugate, a prodrug composed of the anticancer agent sunitinib for renal cell carcinoma and the carrier protein metastin, which are conjugated to each other by a linker. We designed a modified L-homoserine linker, which is composed of an acyl group that acts as the masking group for hydrolysis with an esterase, as well as a carbon chain of appropriate length between sunitinib and metastin. The sunitinib-metastin conjugate was converted into a hydrolyte by hydrolysis of the acyl group with an esterase, and sunitinib was released by intramolecular lactonization. Sunitinib-metastin conjugate, an esterase-sensitive amide prodrug that has a modified L-homoserine linker that participates in the intramolecular lactonization, was synthesized.