- Synthesis of [18F]SU11248, a new potential PET tracer for imaging cancer tyrosine kinase
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N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-[18F]fluoro-2-oxo-1, 2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, a new potential positron emission tomography tracer for imaging cancer tyrosine kinase, has been prepared by the nucleophilic substitution of the nitro-precursor N-[2-(diethylamino)ethyl]-5-[(Z)-(5-nitro-2-oxo-1,2-dihydro-3H- indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide with K 18F/Kryptofix 2.2.2 followed by a simple chromatography methodology combined solid-phase extraction with high-performance liquid chromatography purification procedures in 15-25% radiochemical yields.
- Wang, Ji-Quan,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang
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Read Online
- Novel potent orally active multitargeted receptor tyrosine kinase inhibitors: Synthesis, structure-activity relationships, and antitumor activities of 2-indolinone derivatives
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The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo-fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically (50 nM) and cellularly (50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress.
- Tang, Peng Cho,Su, Yi Dong,Feng, Jun,Fu, Jian Hong,Yang, Jiang Liang,Xiao, Lu,Peng, Jiang Hua,Li, Ya Li,Zhang, Lei,Hu, Bing,Zhou, Ying,Li, Fang Qiong,Fu, Bei Bei,Lou, Li Guang,Gong, Ai Shen,She, Gao Hong,Sun, Wei Hong,Mong, Xian Tai
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Read Online
- Early amidation approach to 3-[(4-amido)pyrrol-2-yl]-2-indolinones
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A new synthesis of 3-[(4-amido)pyrrol-2-yl]-2-indolinones has been developed, where the amide side chain was installed prior to pyrrole formation. This strategy precludes the need to use any coupling reagents to install the amide side chain. This process includes a zinc-free alternative to the Knorr pyrrole synthesis.
- Manley, Jerad M.,Kalman, Monica J.,Conway, Brian G.,Ball, Cynthia C.,Havens, Jeffrey L.,Vaidyanathan, Rajappa
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Read Online
- Synthesis, biological evaluation, and in silico study of pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid derivatives
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A potential molecular hybridization strategy was used to develop 24 novel pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid and amide derivatives. The preliminary in vitro antimicrobial assay delivered four potential derivatives with growth inhibition in the range of 50.87–56.60% at the concentration of 32 μg/ml. In the search of an anticancer candidate, all derivatives were screened by NCI-60 at 10 μM concentration, revealing that 12 derivatives were potential agents against the various types of cancer cell lines, with growth inhibition in the range of 50.21–108.37%. The in vitro cytotoxicity assay against the cell line HEK293 (human embryonic kidney cells) and the hemolysis assay of the representative potent compounds propose their potential for a good therapeutic index. In silico studies of the most potent derivatives qualified their significant pharmacokinetic properties with good predicted oral bioavailability and their adherence to Lipinski's rule of five for druglikeness. A molecular docking study against VEGFR-2 with the best-scored conformations reinforced their anticancer potency. The docking study of the most potent compound against VEGFR-2 with the best-scored conformations displayed a binding affinity (?9.5 kcal/mol) comparable with the drug sunitinib (?9.9 kcal/mol) and exhibited that tighter interactions at the active adenosine triphosphate site might be responsible for anticancer potency.
- Rasal, Nishant K.,Sonawane, Rahul B.,Jagtap, Sangeeta V.
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Read Online
- 5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: Design, synthesis and cytotoxicity against cancer cells
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Angiogenesis plays important roles in tumor growth and metastasis. Sunitinib (Sutent) is an antitumor agent targeting receptor tyrosine kinases which are involved in angiogenesis as well as cancer cell growth and survival. Using the pyridin-3-ol scaffold, which was previously reported as an excellent antioxidant and antiangiogenic platform, we have synthesized sunitinib mimics 6 by hybridizing bicyclic pyridinol 4 as a key scaffold and pyrrole-2-carbaldehydes 7 as side chains. Cytotoxicity assays showed that compounds 6 have comparable to better anticancer activity than sunitinib against five different cancer cell lines. In addition, compounds 6 showed even lower levels of cytotoxicity against normal cells, resulting in up to 26-fold better safety windows, than sunitinib. Signaling pathway-associated transcription factor reporter assay and western blot analyses revealed that apoptosis induction in MDA-MB-231 human breast cancer cells by 6F is mainly mediated through the p53 increase and down-regulation of phospho-signal transducer and activator of transcription 3 (STAT3) and its target gene products, cyclin D, Bcl-2, and survivin. The data strongly suggest that our hybrid compounds can provide a novel anticancer scaffold with improved and safer cytotoxicity profiles than sunitinib.
- Shah, Sajita,Lee, Chaemin,Choi, Hyukjae,Gautam, Jaya,Jang, Hyeonjin,Kim, Geum Jin,Lee, Yu-Jeong,Chaudhary, Chhabi Lal,Park, Sang Won,Nam, Tae-Gyu,Kim, Jung-Ae,Jeong, Byeong-Seon
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Read Online
- Hypochlorite-Mediated Modulation of Photoinduced Electron Transfer in a Phenothiazine–Boron dipyrromethene Electron Donor–Acceptor Dyad: A Highly Water Soluble “Turn-On” Fluorescent Probe for Hypochlorite
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A highly water-soluble phenothiazine (PTZ)–boron dipyrromethene (BODIPY)-based electron donor–acceptor dyad (WS-Probe), which contains BODIPY as the signaling antennae and PTZ as the OCl? reactive group, was designed and used as a fluorescent chemosensor for the detection of OCl?. Upon addition of incremental amounts of NaOCl, the quenched fluorescence of WS-Probe was enhanced drastically, which indicated the inhibition of reductive photoinduced electron transfer (PET) from PTZ to 1BODIPY*; the detection limit was calculated to be 26.7 nm. Selectivity studies with various reactive oxygen species, cations, and anions revealed that WS-Probe was able to detect OCl? selectively. Steady-state fluorescence studies performed at varied pH suggested that WS-Probe can detect NaOCl and exhibits maximum fluorescence in the pH range of 7 to 8, similar to physiological conditions. ESI-MS analysis and 1H NMR spectroscopy titrations showed the formation of sulfoxide as the major oxidized product upon addition of hypochlorite. More interestingly, when WS-Probe was treated with real water samples, the fluorescence response was clearly visible with tap water and disinfectant, which indicated the presence of OCl? in these samples. The in vitro cell viability assay performed with human embryonic kidney 293 (HEK 293) cells suggested that WS-probe is non-toxic up to 10 μm and implicates the use of the probe for biological applications.
- Soni, Disha,Duvva, Naresh,Badgurjar, Deepak,Roy, Tapta Kanchan,Nimesh, Surendra,Arya, Geeta,Giribabu, Lingamallu,Chitta, Raghu
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Read Online
- One-Photon Excitation Followed by a Three-Step Sequential Energy–Energy–Electron Transfer Leading to a Charge-Separated State in a Supramolecular Tetrad Featuring Benzothiazole–Boron-Dipyrromethene–Zinc Porphyrin–C60
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A panchromatic triad, consisting of benzothiazole (BTZ) and BF2-chelated boron-dipyrromethene (BODIPY) moieties covalently linked to a zinc porphyrin (ZnP) core, has been synthesized and systematically characterized by using 1H NMR s
- Badgurjar, Deepak,Seetharaman, Sairaman,D'Souza, Francis,Chitta, Raghu
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supporting information
p. 2184 - 2195
(2020/12/25)
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- BORON-CONTAINING CYCLIC EMISSIVE COMPOUNDS AND COLOR CONVERSION FILM CONTAINING THE SAME
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The present disclosure relates to novel photoluminescent complex comprising a BODIPY moiety covalently bonded to a blue light absorbing moiety, and a color conversion film, a back-light unit using the same.
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Page/Page column 46; 47
(2021/07/24)
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- IMPROVED WAVELENGTH CONVERSION FILM
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Described herein is an improved wavelength conversion film with composite materials that have improved quantum efficiency and color gamut. The film includes narrow FWHM green and red emitting dyes.
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Page/Page column 24
(2021/10/11)
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- Novel enzymatic reduction of α-amido- and α-cyanoalkyl-β-keto esters catalyzed by ketoreductases
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An enzymatic approach for the asymmetric reduction of α-amido- and α-cyanoalkyl-β-keto esters has been developed. We have shown that NADPH-dependent ketoreductases can catalyze these transformations with excellent activity and high stereoselectivity, leading to optically pure β-hydroxy-α-amido esters as well as optically pure β-hydroxy-α-cyanoalkyl esters. With this method tert-butyl 2-acetamido-3-hydroxy-4-methylpentanoate, a valuable chiral intermediate for the synthesis of lactacystin, was obtained in high yield and excellent anti-diastereoselectivity. The ketoreductase catalyzed reduction of α-cyanomethyl- and α-cyanoethyl-β-keto esters to form the corresponding optically pure β-hydroxy esters, which are chiral intermediates for the synthesis of optically pure α-substituted γ-butyro and δ-valerolactams, was accomplished in high yield and high stereoselectivity leading to one stereoisomer out of four (>99 % de, >99 % ee, >99 % conversion).
- Giannopoulos, Vasileios,Myrtollari, Kamela,Smonou, Ioulia,Tyrikos-Ergas, Theodore
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- BORON-CONTAINING CYCLIC EMISSIVE COMPOUNDS AND COLOR CONVERSION FILM CONTAINING THE SAME
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The present disclosure relates to novel photoluminescent complexes comprising a BODIPY moiety covalently bonded to a blue light absorbing moiety, a color conversion film comprising the photoluminescent complex, and a back-light unit using the same.
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Page/Page column 126
(2020/10/21)
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- High-purity L-sunitinib malate preparation method
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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.
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Paragraph 0034; 0037; 0038
(2017/08/28)
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- A method for producing the active MICA environmental protection (by machine translation)
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A active MICA environment-friendly production method, comprises the following steps: oximation, alkylation, chlorinated, ring, process for preparing the intermediate. The invention realizes the recycled, thereby reducing the cost, reduces the amount of waste and waste water; will be S1 in the recrystallization of the sodium acetate as by-product, for S4 in the ring, reducing the waste water and its salt content; in S2 in, now process generally utilizes a potassium carbonate to provide alkaline environment, general in the consumption of 2 more than one equivalent, shortcomings are as follows: a, in the salt in the reaction process too big stirring strenous, b, post-processing needs a large amount of water dissolved inorganic salt, form a large amount of high salt waste water, is changed into the organic base after the solid salt in the reaction process is greatly reduced, post-processing of organic base recycling, reducing the cost and amount of waste water; S3 using batch feeding mode, can be reduced under the same conversion rate, the amount of sulfonyl chloride; S5 recycling reaction generated by-product 2 - mercaptobenzothiazole, recycled in the synthesis of disulphide diphenyl thiazole. (by machine translation)
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Paragraph 0039
(2018/04/01)
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- Spectroscopic and crystallographic investigations of novel Bodipy-derived metal-organic frameworks
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To explore new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-derived metal-organic frameworks (MOFs), we employed 2,6-dicarboxyl-1,3,5,7-tetramethyl-8-phenyl-4,4-difluoroboradiazaindacene (H2L) as a ligand to successfully synthesize five
- Li, Ming,Yao, Yi,Ding, Jie,Liu, Lu,Qin, Jianhua,Zhao, Yaopeng,Hou, Hongwei,Fan, Yaoting
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p. 1346 - 1353
(2015/06/15)
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- Synthesis and in vitro antitumor activity of 1-(3-dimethylamino)propyl indolin-2-one derivatives
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A series of 1-(3-dimethylaminopropyl)indolin-2-one derivatives were designed and synthesized based on the structural features of TMP-20, LK-B030, and BX-517. These newly synthesized derivatives were evaluated for in vitro activity against five human cancer cell lines and three HUVECs. Results revealed that all of the target compounds 1a-h generally show potent activity against these cancer cell lines and higher selectivity on VEGF- and bFGF-stimulated HUVECs than HUVEC. In particular, 1f (IC50s: 1.10-1.47 μM) is 1.8-6.0-fold more potent than sunitinib against MDA-MB-231, A549, HL-60 and K-562, and 1.6-2.8-fold more potent than LK-B030 against MDA-MB-231 and A549.
- Lv, Kai,Wang, Li-Li,Zhou, Xin-Bo,Liu, Ming-Liang,Liu, Hong-Ying,Zheng, Zhi-Bing,Li, Song
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p. 1723 - 1729
(2013/07/26)
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- PROCESS FOR THE PREPARATION OF HIGH PURITY SUNITINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALT
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The present invention relates to an improved process for the preparation of N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide—Sunitinib base of formula (I) and its pharmaceutically acceptable malate salt of formula (I(a)).
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(2011/05/03)
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- Synthesis and antitumor activity of 5-[1-(3-(dimethylamino)propyl)-5- halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3- carboxamides
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We report herein the design and synthesis of novel 1-[3-(dimethylamino) propyl]indolin-2-one derivatives based on the structural features of Sunitinib, a known multitargeted receptor tyrosine kinase inhibitor, and TMP-20, a previously discovered compound with good antitumor activity in our lab. These newly synthesized derivatives were evaluated for in vitro activity against five human cancer cell lines and VEGF/bFGF-stimulated HUVECs. Results revealed that all of the target compounds 1a-p show potent antitumor activity, compounds 1e-h (IC50's: 0.45-5.08 μM) are more active than Sunitinib (IC 50's: 1.35-6.61 μM), and the most active compound 1h (IC 50: 0.47-3.11 μM) is 2.1-4.6-fold more potent than Sunitinib against all five cancer cell lines. In addition, like Sunitinib, 1a-p have higher selectivity on VEGF-stimulated HUVEC other than bFGF-stimulated HUVEC.
- Lv, Kai,Wang, Li-Li,Liu, Ming-Liang,Zhou, Xin-Bo,Fan, Shi-Yong,Liu, Hong-Ying,Zheng, Zhi-Bing,Li, Song
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scheme or table
p. 3062 - 3065
(2011/06/24)
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- Pyrrolo [3,2-C] Pyridine-4-One 2-Indolinone Protein Kinase Inhibitors
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The present invention relates to pyrrolo[3,2-c]pyridine-4-one 2-indolinone compounds of Formula (I) and their pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8X, Y and have the meaning cited in the specification.
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Page/Page column 55
(2010/02/16)
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- In vivo Positron Emission Tomography (PET) imaging of Mesenchymal - Epithelial Transition (MET) receptor
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We report the radiosynthesis and evaluation of 3-[3,5-dimethyl-4-(4-[ 11C]methylpiperazinecarbonyl)-1H-pyrrol-2-ylmethylene]-2-oxo-2, 3-dihydro-1H-indole-5-sulfonic acid (3-chlorophenyl)methylamide, termed [ 11C]SU11274 ([11C]14) for in vivo imaging of mesenchymal - epithelial transition (MET) receptor by positron emission tomography (PET). Following the synthesis of the precursor (13) that was achieved in 10 steps with a total yield of 9.7%, [11C]14 was obtained through radiomethylation in a range of 5-10% radiochemical yield and over 95% radiochemical purity. For in vivo PET studies, two human lung cancer xenograft models were established using MET-positive NCI-H1975 and MET-negative NCI-H520 cell lines. Quantitative [11C]14-PET studies showed that the tumor uptake of [ 11C]14 in the NCI-H1975 xenografts was significantly higher than that in the NCI-H520 xenografts, which is consistent with their corresponding immunohistochemical tissue staining patterns of MET receptors from the same animals. These studies demonstrated that [11C]14-PET is an appropriate imaging marker for quantification of MET receptor in vivo, which can facilitate efficacy evaluation in the clinical development of MET-targeted cancer therapeutics. 2009 American Chemical Society.
- Wu, Chunying,Tang, Zhe,Fan, Weiwen,Zhu, Wenxia,Wang, Changning,Somoza, Edurado,Owino, Norbert,Li, Ruoshi,Ma, Patrick C.,Wang, Yanming
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experimental part
p. 139 - 146
(2010/04/26)
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- PROCESS FOR THE PREPARATION OF N-[2-DIETHYLAMINO)ETHYL]-5-[(5-FLUORO-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL]-2,4-DIMETHYL-1H-PYRROLE-3-CARBOXAMIDE
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The present invention relates to processes for the preparation of N-[2-(Diethylamino) ethyl]-5-[ (5-fluoro-1, 2 -dihydro-2-oxo-3H-indol-3-ylidene) methyl] -2, 4-dimethyl-I H-pyrrole- 3 -carboxamide of formula (VI).
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Page/Page column 18
(2010/12/26)
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- MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS
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The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.
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(2008/06/13)
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- PYRROLO [3,2-C] PYRIDINE-4-ONE 2-INDOLINONE PROTEIN KINASE INHIBITORS
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The present invention relates to pyrrolo[3,2-c]pyridine-4-one 2-indolinone compounds of Formula (I) and their pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8 X , Y and …. have the meaning cited in the specifica
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Page/Page column 72
(2010/11/28)
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- Method of synthesizing indolinone compounds
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Disclosed are methods of preparing pyrrole compounds of formula 14 and indolinone compounds of formula 1 via a synthetic route wherein the amide sidechain on the pyrrole moiety is attached prior to pyrrole formation. The compounds 14 produced by the methods herein are useful in the synthesis of compounds of formula 1, which are useful in the treatment of abnormal cell growth, such as cancer.
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(2010/02/15)
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- PREPARATION OF IMIDAZOLE DERIVATIVES AND METHODS OF USE
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This invention relates to imidazole compounds which are useful in promoting smoking cessation and maintaining abstinence.
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Page/Page column 28-29
(2010/02/14)
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- Combination therapy for the treatment of cancer
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The present invention relates to methods for treatment or prevention of neoplasia disorders using protein tyrosine kinase inhibitors in combination with cyclooxygenase inhibitors, in particular cyclooxygenase-2 selective inhibitors.
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- Prodrugs of a 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
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The present invention relates to pyrrole substituted 2-indolinone compounds and their pharmaceutically acceptable salts which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
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- 5-ARALKYSUFONYL-3-(PYRROL-2-YLMETHYLIDENE)-2-INDOLINONE DERIVATIVES AS KINASE INHIBITORS
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The present invention relates to certain 5-aralkylsulfonyl-3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that inhibit kinases, in particular met kinase. Pharmaceutical compositions comprising these compounds, methods of treating diseases mediated by kinases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing them are also disclosed.
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- 4-aryl substituted indolinones
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The present invention relates to 4-arylindolinones, as well as pharmaceutical compositions thereof, capable of modulating protein kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation. The present invention also relates to methods for treating protein kinase related disorders.
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- Pyrrole substituted 2-indolinone protein kinase inhibitors
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The present invention relates to pyrrole substituted 2-indolinone compounds and their pharmaceutically acceptable salts which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
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- ASYMMETRIC SYNTHESIS. PRACTICAL PRODUCTION OF D AND L THREONINE. DYNAMIC KINETIC RESOLUTION IN RHODIUM AND RUTHENIUM CATALYZED HYDROGENATION OF 2-ACYLAMINO-3-OXOBUTYRATES.
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Enantioselective syntheses of D and L threonine are described.Racemic methyl and ethyl 2-acylamino-3-oxobutyrate 1 were synthesized from the corresponding acetoacetates 6 and then hydrogenated stereoselectively via dynamic kinetic resolution with various chiral P * P Rh(I) 8 and Ru(II) 10 catalysts to give syn optically active alcohols which could be converted by hydrolysis and treatment with propylene oxide into threonine.The best results were obtained using (-) CHIRAPHOS Ru and (+) BINAP Ru as catalysts, in the hydrogenation step leading respectively to D threonine (ee : 99percent) and L threonine (ee : 94percent) in 26-34percent overall yields.
- Genet, J.P.,Pinel, C.,Mallart, S.,Juge, S.,Thorimbert, S.,Laffitte, J.A.
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p. 555 - 567
(2007/10/02)
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- Synthesis and Characterisation of the C30-De-ethylaetioporphyrin Present in Petroleum
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The four de-ethyl analogues of the relatively ubiquitous and biogenetically significant petroporphyrin aetioporphyrin III (3a-d) have been synthesized utilising the ac-biladiene route.A reversed-phase HPLC method of separating a mixture of the four synthe
- Clewlow, Paul J.,Jackson, Anthony H.
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p. 1925 - 1936
(2007/10/02)
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- Derivatives of cephalosporanic acid, processes for their production and their use
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7-[(Carboxymethoximino)-1H-pyrazol-3yl-acetyl]amino-3-desacetoxy-3-(1-methyl-1H-tetrazol-5yl-thio)cephalosporanic acid and salts and solvates thereof which possess chemotherapeutical in particular antibiotic activity.
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- Cephalosporin derivatives and use as antimicrobial agents
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Novel compounds of formula I, STR1 in which R1 is hydrogen, alkyl, phenylalkyl, carbalkoxyalkyl, acyl, carboxyalkyl, alkoxyalkyl, hydroxyalkyl, cyanoalkyl, or carbamoylalkyl, R2 is hydrogen, pivaloyloxymethyl or the residue of an easily splittable ester grouping, R3 is a pyrazolyl radical, unsubstituted or mono- or di-substituted by alkyl, phenyl, alkoxy, alkylthio, carboxy, carboxyalkyl, carbamoyl, carbamoylalkyl, alkylsulphonyl, azido, acylamino, hydrazino, acylhydrazino alkylidenehydrazino, phenylidenehydrazino, in which the phenyl nucleus is unsubstituted or substituted by NH2, lower alkoxy or lower alkyl, furylidenehydrazino, carbalkoxy or a group R5 R6 N--, in which R5 and R6 are the same or different and are hydrogen or alkyl, provided that the nitrogen atoms and the 4-position of the pyrazole nucleus are either unsubstituted or substituted by alkyl, phenyl, or carbalkoxy, and R4 is hydrogen, acetoxy, carbamoyloxy or --S--Rh, in which Rh is a heterocyclic radical.
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- New Efficient Total Syntheses of Derivatives of Protoporphyrin-IX Bearing Deuterated Methyl Groups
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New total syntheses of hemins which are regioselectively deuterated in the 1,5 (2), 5 (3) or 8 (4) methyl groups are described.Syntheses of hemins 2 and 3 follow the progression from pyrromethane 12 to t-butyl tripyrrene-carboxylate hydrobromide (17 and 30) and then to a,c-biladiene dihydrobromide (19 and 31), but for reasons of economy in use of labeled monopyrroles, the a,c-biladiene dihydrobromide 40 for hemin 4 is approached in an initially "clockwise" manner by synthesis of a benzyl tripyrrene-carboxylate hydrobromide 37 from the pyrromethane 5.Cyclization of the a,c-biladienes (19, 31, and 40) was accomplished by brief heating in dimethylformamide in the presence of copper(II) chloride.
- Smith, Kevin M.,Pandey, Ravindra K.
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p. 1383 - 1388
(2007/10/02)
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