- Identification of a new series of benzothiazinone derivatives with excellent antitubercular activity and improved pharmacokinetic profiles
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Nitrobenzothiazinone (BTZ) is a promising scaffold with potent activity against M. tuberculosis by inhibiting decaprenylphosphoryl-beta-d-ribose 2′-oxidase (DprE1). But unfavorable durability poses a challenge to further development of this class of agents. Herein, a series of BTZs bearing a variety of different substituents at the C-2 position were designed and synthesized. Compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Ra and were profiled for metabolic stability, plasma protein-binding capacity and pharmacokinetics in vivo. In general, these new BTZs containing N-piperazine, N-piperidine or N-piperidone moiety have excellent antitubercular activity and low cytotoxicity. Several of the compounds showed improved microsomal stability and lower plasma protein-binding, opening a new direction for further lead optimization. And we obtained compound 3o, which maintained good anti-tuberculosis activity (MIC = 8 nM) and presented better in vitro ADME/T and in vivo pharmacokinetic profiles than reported BTZ compound PBTZ169, which may serve as a candidate for the treatment of tuberculosis.
- Xiong, Lu,Gao, Chao,Shi, Yao-Jie,Tao, Xin,Rong, Juan,Liu, Kun-Lin,Peng, Cui-Ting,Wang, Ning-Yu,Lei, Qian,Zhang, Yi-Wen,Yu, Luo-Ting,Wei, Yu-Quan
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p. 11163 - 11176
(2018/03/26)
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- DUAL NAV1.2/5HT2A INHIBITORS FOR TREATING CNS DISORDERS
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Compounds of formula I: I are disclosed, as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disorders in a patient in need are also disclosed. Such disorders include depression, bipolar disorder, pain, schizophrenia, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, autism, a cognitive impairment, or a neuropsychiatric symptom such as apathy, depression, anxiety, psychosis, aggression, agitation, impulse control disorders, and sleep disorders in neurological disorders such as Alzheimer's and Parkinson's diseases.
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Paragraph 0296
(2018/03/28)
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- A COMPOUND AND A PHARMACEUTICAL COMPOUND FOR TREATMENT OF INFLAMMATORY DISEASES
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The present invention relates to a compound and a pharmaceutical composition for treating inflammatory diseases, and the present invention is characterized by being a compound represented by chemical formula I or a pharmaceutically acceptable salt, hydrat
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Paragraph 0089-0092
(2016/10/09)
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- ETHER DERIVATIVES
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The present invention relates to ether derivatives according to general formula I, and to their pharmaceutically-acceptable salts, which may be used in treating or preventing cognitive disorders, drug addiction, depression, anxiety, drug dependence, demen
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Page/Page column 13-14
(2008/06/13)
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- PIPERIDINE DERIVATIVES AND THEIR USE AS SELECTIVE INHIBITORS OF MIP-1ALPHA BINDING TO ITS RECEPTOR CCR1
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A compound of the formula (I) wherein a, b, c R1, R2, R3, R4, R5, R6, R7, Q, W, Y, and Z are defined as above , useful as potent and selective inhibitors of MIP-1α (CCL3) binding to its receptor CCR1 found on inflammatory and immunomodulatory cells (preferably leukocytes and lymphocytes).
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