Structure of Gefitinib

Tanaka, Rumiko; Haramura, Masayuki; Tanaka, Akito; Hirayama, Noriaki

doi:10.2116/analscix.20.x173

Cited by 11 publications

(8 citation statements)

References 3 publications

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“…As a consequence of the protonation at atom N3 of the pyrimidine ring in (II), the intra-ring angle at N3 is about 6.2 larger than in (I), while the intra-ring angles at C20 and C21 decrease by about 4.9 and 4.6 , respectively. A similar trend is seen in the crystal structures of erlotinib and its salts Selvanayagam et al, 2008) and ErbB2 inhibitor and its salts (Li et al, 2006), and is also comparable with the trend in geftinib (Tanaka et al, 2004).…”

Section: Figuresupporting

confidence: 79%

“…This results in a widening of the three interior bond angles (C11-N1-C14, N2-C14-N1 and N1-C11-C12) of the above-described ring by about 6 and a narrowing of the exterior angle (C10-C11-N1) by 4 , when compared with the corresponding values in (II) ( Table 2). These features are also observed and found to be similar in geftinib (Tanaka et al, 2004) and erlotinib salt structures (Selvanayagam et al, 2008;Sridhar et al, 2010) (see Scheme).…”

Section: Figurementioning

confidence: 58%

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Tosylate salts of the anticancer drug lapatinib

et al. 2013

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Two tosylate salts of an anticancer drug lapatinib, viz. a monotosylate [systematic name: ({5-[4-({3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)quinazolin-6-yl]furan-2-yl}methyl)[2-(methylsulfonyl)ethyl]azanium 4-methylbenzenesulfonate], C29H27ClFN4O4S(+)·C7H7O3S(-), (I), and a ditosylate [systematic name: 4-({3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}amino)-6-]5-({[2-(methylsulfonyl)ethyl]azaniumyl}methyl)furan-2-yl[quinazolin-1-ium bis(4-methylbenzenesulfonate)], C29H28ClFN4O4S(2+)·2C7H7O3S(-), (II), were obtained during crystallization attempts for polymorphism. In both structures, the lapatinib cation is in a distorted U-like conformation and the tosylate anion is clamped between the aniline N atom and methylamine N atom through N-H···O hydrogen bonds, forming an R2(2)(15) ring motif. The 4-anilinoquinazoline ring system is essentially planar in (I), while it is twisted in (II), controlled by an intramolecular C-H···N interaction. In (I), alternating cations and anions are linked by N-H···O hydrogen bonds into C2(2)(6) chains. These chains are linked by cations in a helical manner. The presence of the additional tosylate anion in (II) results in the formation of one-dimensional tapes of fused hydrogen-bonded rings through N-H···O and C-H···O interactions. These studies augment our understanding of the role of nonbonded interactions in the solid state, which is useful for correlation to the physicochemical properties of drug products.

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Section: Figuresupporting

confidence: 79%

Section: Figurementioning

confidence: 58%

Tosylate salts of the anticancer drug lapatinib

et al. 2013

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“…It matches form I (CCDC No. 259805) 17 of the drug as confirmed by the simulated PXRD pattern. Isonicotinamide was purchased from Sigma-Aldrich, India, as anhydrous crystalline powders with >99% purity, whereas vanillin was purchased from HiMedia, India.…”

Section: Methodsmentioning

confidence: 53%

“…tacts. 24,17 Single-crystal X-ray diffraction of GEF-VAN revealed that the drug and coformer cocrystallized in a 2:1 stoichiometric ratio in the triclinic space group P1 (Figure S4a The quinazoline rings of the dimer are in proximity but are antioriented due to morpholine rings of each GEF molecule lying at opposite ends. This orientation of the GEF molecules allowed the accommodation of the coformer through the above-mentioned hydrogen bonding.…”

Section: Resultsmentioning

confidence: 99%

Novel Pharmaceutical Cocrystals of Gefitinib: A Credible Upswing in Strategic Research to Ameliorate Its Biopharmaceutical Challenges

Pandit

Chadha

Laha

et al. 2022

Crystal Growth & Design

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There is a paradigm shift in the preformulation drug development strategy of the pharmaceutical industry to engineer the desired dosage form by solid-state manipulation. Cocrystallization is one approach that has been applied in the present study to fortify the poor biopharmaceutical attributes of one of the leading orally effective anticancer drugs in chemotherapy, Gefitinib (GEF). Two novel pharmaceutical cocrystals were engineered with Generally Regarded as Safe (GRAS) status coformers isonicotinamide (INCT) and vanillin (VAN). These novel cocrystals were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), fourier transform infrared (FTIR) spectrometry, hot stage microscopy (HSM), field emission scanning electron microscopy (FESEM), and single-crystal X-ray diffraction (SXRD). Crystal structure analysis showed that GEF− VAN had cocrystallized in a 2:1 ratio, whereas in the case of the cocrystal hydrate of Gefitinib with isonicotinamide (GEF−INCT) the asymmetric unit showed a stoichiometric ratio of drug/coformer/water of 1:1:2. Both cocrystals showed improvement in intrinsic dissolution, maximal serum concentration, and cell inhibition response as compared to a drug, with GEF−INCT•2H 2 O showing better results than GEF−VAN. Such an improvement of biopharmaceutical properties with good stability via these new solid forms of GEF produced by cocrystallization strengthens the claim of novel drug formulation.

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“…When we analyzed the EDX data of drug-loaded nanoparticles, the ratio of Ca/C/O was not ~1:1:3, and the elemental percentage of calcium was less than that of the CSCaCO 3 NP which suggests the presence of other elements which could be due to the surface functionalization with the drugs. It is interesting to note that when GEF with the molecular formula of C 22 H 24 ClNFN 4 O 3 [ 87 ] was analyzed, oxygen (10.85%), carbon (68.33%), nitrogen (14.02%), fluorine (4.05%), and chlorine (2.28%) were obtained. For PTXL, with the molecular formula C 47 H 51 NO 14 [ 88 ], only oxygen (16.37%) and carbon (80.63%) were inferred from the spectra, where the N peak could not be observed, even after repeated measurements at different sites.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of Gefitinib and Paclitaxel Mono and Dual Drug-Loaded Blood Cockle Shells (Anadara granosa)-Derived Aragonite CaCO3 Nanoparticles

et al. 2021

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Calcium carbonate has slowly paved its way into the field of nanomaterial research due to its inherent properties: biocompatibility, pH-sensitivity, and slow biodegradability. In our efforts to synthesize calcium carbonate nanoparticles (CSCaCO3NP) from blood cockle shells (Anadara granosa), we developed a simple method to synthesize CSCaCO3NP, and loaded them with gefitinib (GEF) and paclitaxel (PTXL) to produce mono drug-loaded GEF-CSCaCO3NP, PTXL-CSCaCO3NP, and dual drug-loaded GEF-PTXL-CSCaCO3NP without usage of toxic chemicals. Fourier-transform infrared spectroscopy (FTIR) results reveal that the drugs are bound to CSCaCO3NP. Scanning electron microscopy studies reveal that the CSCaCO3NP, GEF-CSCaCO3NP, PTXL-CSCaCO3NP, and GEF-PTXL-CSCaCO3NP are almost spherical nanoparticles, with a diameter of 63.9 ± 22.3, 83.9 ± 28.2, 78.2 ± 26.4, and 87.2 ± 26.7 (nm), respectively. Dynamic light scattering (DLS) and N2 adsorption-desorption experiments revealed that the synthesized nanoparticles are negatively charged and mesoporous, with surface areas ranging from ⁓8 to 10 (m2/g). Powder X-ray diffraction (PXRD) confirms that the synthesized nanoparticles are aragonite. The CSCaCO3NP show excellent alkalinization property in plasma simulating conditions and greater solubility in a moderately acidic pH medium. The release of drugs from the nanoparticles showed zero order kinetics with a slow and sustained release. Therefore, the physico-chemical characteristics and in vitro findings suggest that the drug loaded CSCaCO3NP represent a promising drug delivery system to deliver GEF and PTXL against breast cancer.

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Structure of Gefitinib

Cited by 11 publications

References 3 publications

Tosylate salts of the anticancer drug lapatinib

Tosylate salts of the anticancer drug lapatinib

Novel Pharmaceutical Cocrystals of Gefitinib: A Credible Upswing in Strategic Research to Ameliorate Its Biopharmaceutical Challenges

Synthesis and Characterization of Gefitinib and Paclitaxel Mono and Dual Drug-Loaded Blood Cockle Shells (Anadara granosa)-Derived Aragonite CaCO3 Nanoparticles

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