123910-88-3Relevant academic research and scientific papers
Multi-arm polymeric prodrug conjugates of pemetrexed-based compounds
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Page/Page column 30, (2020/08/30)
Among other aspects, provided herein are multi-arm polymeric prodrug conjugates of pemetrexed-based compounds. Methods of preparing such conjugates as well as methods of administering the conjugates are also provided. Upon administration to a patient, release of the pemetrexed-based compound is achieved.
Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives
Balaraman, Selvakumar,Nayak, Nagaraj,Subbiah, Madhuri,Elango, Kuppanagounder P.
, p. 2538 - 2546 (2018/11/10)
A series of ten new compounds (7a–j) has been synthesized by absolutely replacing the glutamic acid part of Pemetrexed drug, chemically known as N-{4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-l-glutamic acid, with primary, secondary, and aryl amines in high yields using diethylphosphorocyanidate (DEPC) as a peptide coupling agent. All the synthesized compounds are characterized by 1H and 13C NMR, LCMS, and FT-IR spectral techniques. All the synthesized novel non-glutamate 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives showed 4- to 7-folds higher antiviral activity than its structurally similar commercial drug Pemetrexed against Newcastle disease virus, an avian paramyxovirus. Among the lot, compounds possessing carboxamide synthesized using five-membered heteroaryl amines (7i and 7j) exhibited the highest antiviral activity. [Figure not available: see fulltext.].
Contrast agents for applications including perfusion imaging
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Page/Page column 31; 32, (2016/09/12)
The present invention is directed, in part, to compounds and methods for imaging the central nervous system or cancer, comprising administering to a subject a contrast agent which comprises a compound that binds MC-I, and an imaging moiety, and scanning the subject using diagnostic imaging.
INHIBITORS OF HISTONE LYSINE SPECIFIC DEMETHYLASE (LSD1) AND HISTONE DEACETYLASES (HDACS)
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Page/Page column 130, (2015/09/28)
A series of phenelzine analogs comprising a phenelzine scaffold linked to an aromatic moiety and their use as inhibitors of lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) is provided. The presently disclosed phenelzine analogs exhibit potency and selectivity for LSD1 versus MAO and LSD2 enzymes and exhibit bulk, as well as, gene specific histone methylation changes, anti-proliferative activity in several cancer cell lines, and neuroprotection in response to oxidative stress. Accordingly, the presently disclosed phenelzine analogs can be used to treat diseases, conditions, or disorders related to LSD1 and/or HDACs, including, but not limited to, cancers and neurodegenerative diseases.
1-Acetyl-2,3-dimethylimidazolidine: A novel organic reductant for transfer hydrogenation
Li, Donghong,Zhang, Yongbin,Zhou, Guofu,Guo, Wei
, p. 225 - 228 (2008/12/20)
1-Acetyl-2,3-dimethylimidazolidine was synthesized and was shown to be able to directly reduce a series of aromatic, aliphatic and α,β- unsaturated aldehydes as well as imines in high yields. Georg Thieme Verlag Stuttgart.
Synthesis and biological evaluation of pyridazinone analogues as potential cardiac positron emission tomography tracers
Purohit, Ajay,Radeke, Heike,Azure, Michael,Hanson, Kelley,Benetti, Richard,Su, Fran,Yalamanchili, Padmaja,Yu, Ming,Hayes, Megan,Guaraldi, Mary,Kagan, Mikhail,Robinson, Simon,Casebier, David
experimental part, p. 2954 - 2970 (2009/05/27)
A series of fluorinated pyridazinone derivatives with IC50 values ranging from 8 to 4000 nM for the mitochondrial complex 1 (MC1) have been prepared. Structure-activity relationship (SAR) assessment indicated preference of the fluorine label to be incorporated on an alkyl side chain rather than directly on the pyridazinone moiety. Tissue distribution studies of a series of analogues ([18F] 22-28) in Sprague-Dawley (SD) rats identified [ 18F]27 as the most promising radiotracer with high uptake in cardiac tissue (3.41%ID/g; 30 min post injection) in addition to favorable heart to nontarget organ distribution ratios. MicroPET images of SD rats and nonhuman primates after [18F]27 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.
Synthesis and biological evaluation of the mitochondrial complex 1 inhibitor 2-[4-(4-fluorobutyl)benzylsulfanyl]-3-methylchromene-4-one as a potential cardiac positron emission tomography tracer
Radeke, Heike,Hanson, Kelley,Yalamanchili, Padmaja,Hayes, Megan,Zhang, Zhi-Qin,Azure, Michael,Yu, Ming,Guaraldi, Mary,Kagan, Mikhail,Robinson, Simon,Casebier, David
, p. 4304 - 4315 (2008/03/12)
A series of fluorinated chromone analogs with IC50 values ranging from 9 to 133 nM for the mitochondrial complex I (MC-I) has been prepared. A structure-activity relationship (SAR) study of the most potent fluorinated chromone analog 10 demonstrated the linkage heteroatom preference of the side chain region of the molecule while maintaining potent MC-I inhibitory activity. Tissue distribution studies 30 min after [18F]10 administration to Sprague-Dawley (SD) rats demonstrated high uptake of the radiotracer from the blood pool into the myocardium (2.24% ID/g), kidney (1.93% ID/g), and liver (2.00% ID/g). After 2 h about 66% of the activity in the myocardium at 30 min had been retained, whereas ～70% had been cleared from the liver and kidney. MicroPET images of SD rats after [18F]10 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.
Contrast agents for myocardial perfusion imaging
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Page/Page column 43, (2008/06/13)
The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.
Contrast agents for myocardial perfusion imaging
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Page/Page column 16, (2010/02/13)
The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.
Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates
Gangjee, Aleem,Zeng, Yibin,McGuire, John J.,Mehraein, Farideh,Kisliuk, Roy L.
, p. 6893 - 6901 (2007/10/03)
Bridge homologation of the previously reported classical two-carbon-bridged antifolates, a 5-substituted 2,4-diaminofuro[2,3-d]pyrimidine (1) [which is a 6-regioisomer of LY231514 (Alimta)] and a 6-subsituted 2-amino-4-oxopyrrolo[2,3- d]pyrimidine, afforded the three-carbon-bridged antifolates analogues 4 and 5, with enhanced inhibitory activity against tumor cells in culture (EC 50 values in the 10-8-10-7 M range or less). These two analogues were synthesized via a 10-step synthetic sequence starting from methyl 4-bromobenzoate (14), which was elaborated to the α-chloromethyl ketone (8) followed by condensation with 2,6-diamino-pyrimidin-4-one (7) to afford the substituted furo[2,3-d]pyrimidine 9 and the pyrrolo[2,3-d]-pyrimidine 10. Subsequent coupling of each regioisomer with diethyl-L-glutamate followed by saponification afforded 4 and 5. The biological results indicate that elongation of the C8-C9 bridge of the classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidine and 6-substituted 2-amino-4-oxopyrrolo[2,3-d]pyrimidine are highly conducive to antitumor activity in vitro, despite a lack of increase in inhibitory activity against the target enzymes. This supports our original hypothesis that truncation of the B-ring of a highly potent 6-6 ring system to a 6-5 ring system can be compensated by bridge homologation to restore the overall length of the molecule.
