- Design, synthesis and biological evaluation of novel thiohydantoin derivatives as potent androgen receptor antagonists for the treatment of prostate cancer
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Prostate cancer (PC) is the most common malignancy in men worldwide. Here, two series of novel thiohydantoin derivatives of enzalutamide as potent androgen receptor (AR) antagonists were designed and synthesized. Among them, compound 31c was identified as an AR antagonist which is 2.3–fold more potent than enzalutamide. Molecular docking studies were performed to explain the improved potency of 31c at AR. In cell proliferation assays, 31c exhibited similar anti-proliferative activities with enzalutamide against hormone sensitive LNCaP cells and AR-overexpressing LNCaP/AR cells. These data indicate that 31c can be a good lead compound for further structure optimization for the treatment of prostate cancer.
- Wang, Ao,Wang, Yawan,Meng, Xin,Yang, Yushe
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- THIENODIAZEPINE DERIVATIVES AND APPLICATION THEREOF
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The present invention relates to a class of thienodiazepine derivatives and an application thereof in the preparation of a drug for the treatment of diseases associated with bromodomain and extra-terminal (BET) Bromodomain inhibitors. Specifically, the present invention relates to compounds represented by formulas (I) and (II), as well as pharmaceutically acceptable salts thereof.
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Paragraph 0310; 0313-0314
(2020/08/09)
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- Synthesizing method of 5-fluoro-3-methyl isobenzofuran-1(3H)-ketone
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The invention relates to the technical field of medicine and relates to a synthesizing method of 5-fluoro-3-methyl isobenzofuran-1(3H)-ketone. The 5-fluoro-3-methyl isobenzofuran-1(3H)-ketone is synthesized by subjecting the initial raw material phthalimide to 8 steps such as nitration, reduction, cyclizing, diazotization, bromination and esterification. The method has the advantages that the preparation of the 5-fluoro-3-methyl isobenzofuran-1(3H)-ketone which is the key intermediate of the antitumor drug Lorlatinib (PF-06463922), total yield can reach 7.0% or above, and the method is simpleto operate, convenient in post-processing, low in time consumption, low in cost and beneficial to industrialization; the Lorlatinib is synthesized by subjecting the intermediate and 1-methyl-3-(( methylamino)methyl)-1H-pyrazol-5-nitrile to ammonolysis, substitution, coupling, chiral resolution and the like, and a new method is provided for the synthesizing of the antitumor drug Lorlatinib.
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Paragraph 0039; 0046-0048
(2019/01/23)
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- Preparation method of novel isobenzofuranone intermediate
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The invention discloses a synthetic method of an important intermediate of novel diuretic drug ROMK inhibitor. The synthetic method comprises the following steps: adopting 4-nitro phthalimide as the starting material, performing two-step reaction, diazotization reaction, Suzuki reaction and epoxidation reaction, thus obtaining the important intermediate 5-epoxy ethyl isobenzofuranone of the ROMK inhibitor. The preparation method provided by the invention is mild in route reaction conditions, simple in after-treatment, high in yield, and capable of avoiding the use of toxic gases and bioenzymecatalysts.
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- The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives
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The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several compounds demonstrated highly efficacious immunosuppressive properties, especially compounds 2d, 2e, 2h and 2j, which were superior to MPA, while compounds 2k, 2m, 2n, 4c and 5d exhibited an equipotent inhibitory activity compared to MPA. Generally, it was obviously demonstrated that α,β-unsaturated amides proved more potent than the diamide and urea series. The present study provides a guide for further research on development of safe and effective immunosuppressive agents.
- Yang, Na,Wang, Qing-He,Wang, Wen-Qian,Wang, Jian,Li, Feng,Tan, Shen-Peng,Cheng, Mao-Sheng
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- LIGHT-DRIVEN ROTARY MOLECULAR MOTORS
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Compounds of Formula (1) are disclosed. Cb is a carbocyclic or heterocyclic group having an atom within the cyclic structure selected from C, N, Si, and Cr and singly bound to A. A is CR, COR, CSR, CNR2, CCN, CCONR2, CNO2, CNNAr, CX′, or N. Cr is a chromophore having a substantially planar cyclic structure. The compounds function as nanometer-scale rotary molecular motors powered and controlled by light energy. The design of the molecular motor devices is flexible so that the rotary direction, drive light wavelength, and other physical characteristics can be varied. The compounds can be chemically functionalized to allow it to be integrated into or attached to a variety of structures. The device can be used in applications where mechanical power, positional control, and information encoding are to be generated at the size scale of individual molecules.
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- PROCESSES FOR THE PREPARATION OF CITALOPRAM AND ITS INTERMEDIATE 5-AMINOPHTHALIDE
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The invention relates to processes for the preparation of 5-amino-2-benzofuran- l(3H)-one of Formula (I), and to the use of this compound as an intermediate for the preparation of citalopram. The invention also relates to a process for the preparation of citalopram or a salt thereof, and pharmaceutical compositions that include the citalopram or a salt thereof.
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Page/Page column 8-9
(2010/11/24)
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- A concise, regio and stereoselective route to fluorinated protoberberines via tandem addition-cyclisation reactions of phthalide anions with 3,4-dihydroisoquinolines
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A series of fluorinated protoberberines have been prepared by condensing fluorinated phthalide anions with 6,7-dimethoxydihydroisoquinoline. The spectroscopy and stereochemistry of the products are discussed and the stereochemical outcome of the reactions rationalised.
- Warrener, Ronald N.,Liu, Ligong,Russell, Richard A.
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p. 7485 - 7496
(2007/10/03)
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- Anti-inflammatory phthalazinones
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A compound useful as anti-inflammatory agents in warm-blooded animals of the formula STR1 wherein X is a member of the class of ethylene and ethenyl and is substituted for hydrogen in the sixth or seventh position of the 1(2H)-phthalazinone ring Y is a member of the class of hydrogen and hydroxyl R1 is a member of the class of hydrogen, alkyl, alkoxy, hydroxyl, halogen, nitro, --NR3 R4, --COR5 and --O--A wherein A is a mineral acid residue which with --O-- forms an ester or the alkali metal salt of said ester, R2 is a member of the class of hydrogen, alkyl, phenyl, substituted phenyl, heteroaryl, hydroxyalkylene, polyhydroxyalkylene, aminoalkylene, alkylaminoalkylene, and carboxyalkylene, R3, R4 are independently from the class of hydrogen, alkyl, aminoalkylene or alkylaminoalkylene, R5 is a member of the class of OR3 and STR2 for example hydroxyl, methoxyl, 2-dimethylaminoethoxyl or 2-dimethylaminoethylamino, and wherein by alkyl and alkylene is meant respectively a mono- or divalent saturated aliphatic radical containing up to about eight carbon atoms, wherein the nitrogen of the alkylamino or alkylaminoalkylene may form a heterocycle with the alkyl or alkylene groups, wherein substituted phenyl may be substituted by, for example, alkyl, hydroxyl, alkoxy, halogen, nitro or amino, wherein heteroaryl may be, for example, 2-pyridyl.
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