- Method for preparing MPTF-E (meptazinol E)
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The invention discloses a method for preparing MPTF-E (meptazinol E), and belongs to the technical field of chemical drug preparation. The method comprises the following steps: (1) chloroanisole reacts with N-methylcaprolactam, and a compound I is obtained; (2) the compound I reacts with iodoethane, and a compound II is obtained; (3) boron bromide reacts with the compound II, and a compound III is obtained; (4) the compound III reacts with bromobutane, and a compound IV is obtained; (5) the compound IV is dissolved in anhydrous THF (tetrahydrofuran), lithium aluminum hydride is added, reaction reflux is performed, reactants are cooled to the room temperature, H2O is slowly added to a reaction liquid, then MgSO4 is added for stirring, filtration, reduced-pressure distillation and purification are performed, and a compound V is obtained. The method has the following advantages that MPTF-E is synthesized for the first time, and qualified impurity E comparison products are provided for meptazinol; a reagent adopted is a common solvent and easy to obtain; safe solvents such as ethyl acetate, petroleum ether and the like are used for treatment and have low toxicity; the process is simple and easy to operate, little energy is consumed, the stability is high, and the purity is high.
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- Method of treating cancer
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The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.
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- Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents
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A series of novel diaryl ether lactams have been identified as very potent dual inhibitors of protein farnesyltransferase (FTase) and protein geranylgeranyltransferase I (GGTase-I), enzymes involved in the prenylation of Ras. The structure of the complex formed between one of these compounds and FTase has been determined by X-ray crystallography. These compounds are the first reported to inhibit the prenylation of the important oncogene Ki-Ras4B in vivo. Unfortunately, doses sufficient to achieve this endpoint were rapidly lethal.
- DeSolms, S. Jane,Ciccarone, Terrence M.,MacTough, Suzanne C.,Shaw, Anthony W.,Buser, Carolyn A.,Ellis-Hutchings, Michelle,Fernandes, Christine,Hamilton, Kelly A.,Huber, Hans E.,Kohl, Nancy E.,Lobell, Robert B.,Robinson, Ronald G.,Tsou, Nancy N.,Walsh, Eileen S.,Graham, Samuel L.,Beese, Lorena S.,Taylor, Jeffrey S.
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p. 2973 - 2984
(2007/10/03)
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- Inhibitors of prenyl-protein transferase
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The present invention is directed to azepan-2-one compounds which inhibit prenyl-protein transferase, particularly farnesyl-protein transferase (Ftase), and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
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- 2-Bromo-3-methoxycyclohex-2-enone, a New Reagent for the α-Arylation of Lactams
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We report efficient syntheses of 2-bromo and 2-chloro-3-methoxycyclohex-2-enone and their use as m-hydroxyphenyl cation synthons for the α-arylation of lactams.The sequence has been used to synthesize the analgesic drug meptazinol.
- Shepherd, Robin G.,White, Alan C.
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p. 2153 - 2156
(2007/10/02)
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- Process for making m-hydroxyphenyl substituted compounds
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m-Hydroxyphenyl substituted compounds of formula STR1 where R is an organic radical and R1 is hydroen or an organic radical are prepared by dehydrohalogenating a compound of formula STR2 (where X is chlorine or bromine, and R and R1 have the above meanings). Preferred novel starting materials of formula (II) are of the formula STR3 (where R1 and X are as above, n is 2,3 or 4, R2 is hydrogen or lower alkyl and R3 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl).
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- Hexahydroazepine, piperidine and pyrrolidine derivatives
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The invention concerns novel 2-oxo-hexahydroazepine, -piperidine and -pyrrolidine derivatives of formula (I) and their aromatized derivatives of formula (II) STR1 where n is 2, 3 or 4, R is hydrogen, lower alkyl or aryl(lower)alkyl, R2 is hydrogen, lower alkyl or aryl(lower)alkyl and R3 is hydrogen, lower alkyl, aryl(lower)alkyl, lower alkenyl or lower alkynyl. The compounds are useful as intermediates for preparing 3,3-disubstituted -hexahydroazepine, -piperidine and -pyrrolidine compounds having pharmacological activity, particularly analgesic activity.
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- Hexahydroazepine, piperidine and pyrrolidine derivatives
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The invention concerns novel 2-oxo-hexahydroazepine, -piperidine and -pyrrolidine of formula I STR1 where n is 2,3 or 4, R is hydrogen, lower alkyl or aryl(lower)alkyl and R1 is lower alkyl. The compounds may be aromatized and the aromatized compounds converted to 3,3-disubstituted-hexahydroazepine, -piperidine and -pyrrolidine compounds having pharmacological activity, particularly analgesic activity.
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