- 2-bromo-5- fluorine three fluorine methylbenzene preparation method
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The invention discloses a method for preparing 2-bromine-5-trifluorotoluene chloride. The method comprises the following step: under an anhydrous condition and in an organic solvent, performing cracking reaction on an anhydrous compound 1 or a compound 1', thereby preparing 2-bromine-5-trifluorotoluene chloride. According to the method, the reaction of an upper amino protecting group of m-trifluoromethyl phenylamine, the bromination reaction and the reaction of removing the amino protecting group can be all performed in one same reaction kettle without transferring or storing materials. The raw materials used in the method disclosed by the invention are cheap and easy to obtain, the reaction step is short, the reaction condition is gentle, the utilization rate of bromine is high, and the positioning selectivity of bromine feeding is high, so that a final product is low in isomeride impurity, high in reaction conversion rate, high in yield, high in product purity, low in production cost is low and applicable to industrialization production. The compound 1 and compound 1' are as shown in the specification.
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- PROCESS FOR THE PREPARATION OF SUBSTITUTED BENZOTRIHALIDE
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The present invention provides a process for the preparation of compound of Formula I; wherein X is selected from the group consisting of fluorine, chlorine, bromine and iodine; Y is selected from X and -NR1R2; R1 and R1, independent of each other, are selected from the group consisting of hydrogen, C1-4 alkyl and –COR; R is C1-4 alkyl.
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Page/Page column 7
(2016/06/06)
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- HETEROCYCLYC SULFONAMIDES HAVING EDG-I ANTAGONISTIC ACTIVITY
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The invention relates to chemical compounds of formula (I), (Ia) and (Ib) or pharmaceutically acceptable salts thereof, which possess Edg-1 antagonistic activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an anti-cancer effect in a warm-blooded animal, such as man.
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Page/Page column 187
(2008/12/05)
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- Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators
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Pharmacokinetic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. Subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential.
- Hamann, Lawrence G.,Manfredi, Mark C.,Sun, Chongqing,Krystek Jr., Stanley R.,Huang, Yanting,Bi, Yingzhi,Augeri, David J.,Wang, Tammy,Zou, Yan,Betebenner, David. A.,Fura, Aberra,Seethala, Ramakrishna,Golla, Rajasree,Kuhns, Joyce E.,Lupisella, John A.,Darienzo, Celia J.,Custer, Laura L.,Price, Jennifer L.,Johnson, James M.,Biller, Scott A.,Zahler, Robert,Ostrowski, Jacek
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p. 1860 - 1864
(2008/02/04)
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- Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure-activity relationships of 2-piperazin-1-yl-1H- benzimidazoles
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The vanilloid receptor-1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2- ylpiperazin-1-yl)-1H-benzo-[d]imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant (CFA).
- Ognyanov, Vassil I.,Balan, Chenera,Bannon, Anthony W.,Bo, Yunxin,Dominguez, Celia,Fotsch, Christopher,Gore, Vijay K.,Klionsky, Lana,Ma, Vu V.,Qian, Yi-Xin,Tamir, Rami,Wang, Xianghong,Xi, Ning,Xu, Shimin,Zhu, Dawn,Gavva, Narender R.,Treanor, James J. S.,Norman, Mark H.
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p. 3719 - 3742
(2007/10/03)
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- BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS VANILLOID RECEPTOR LIGANDS
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Compounds of formula (I) are useful in the treatment of vanilloid-receptor-meditated diseases, such as inflammatory or neuropathic pain and diseases involving sensory nerve function such as asthma, rheumatoid arthritis, osteoarthritis, inflammatory bowel disorders, urinary incontinence, migraine and psoriasis.
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