- Identification of Better Pharmacokinetic Benzothiazinone Derivatives as New Antitubercular Agents
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A series of new 8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one(BTZ) derivatives containing a C-2 nitrogen spiro-heterocycle moiety based on the structures of BTZ candidates BTZ043 and PBTZ169 were designed and synthesized as new antitubercular agents. Many of them were found to have excellent in vitro activity (MIC 0.15 μM) against the drug susceptive Mycobacterium tuberculosis H37Rv strain and two clinically isolated multidrug-resistant strains. Compounds 11l and 11m display acceptable safety, greater aqueous solubility, and better pharmacokinetic profiles than PBTZ169, suggesting their promising potential to be lead compounds for future antitubercular drug discovery.
- Lv, Kai,You, Xuefu,Wang, Bin,Wei, Zengquan,Chai, Yun,Wang, Bo,Wang, Apeng,Huang, Guocheng,Liu, Mingliang,Lu, Yu
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p. 636 - 641
(2017/06/13)
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- Spirocyclic derivatives
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The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease, disorder or condition ameliorated by inhibition of a dopamine transporter); and methods of treating patients with such compounds; wherein R1, R2, R3, R4, R5, R6, R9, R10, Q, X, Y, Z, A, L, B, m, n and p are as defined herein.
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Page/Page column 207
(2016/04/09)
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- SUBSTITUTED DIAZA-SPIRO-[4.5]-DECANE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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This invention concerns substituted diaza-spiro-[4.5]-decane derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK2 antagonist ic activity, a combined NK1/NK3 antagonist ic activity and a combined NK1/NK2/NK3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment and/or prophylaxis of schizophrenia, emesis, anxiety and depression, irritable bowel syndrome (IBS), circadian rhythm disturbances, pre-eclampsia, nociception, pain, in particular visceral and neuropathic pain, pancreatitis, neurogenic inflammation, asthma, chronic obstructive pulmonary disease (COPD) and micturition disorders such as urinary incontinence. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.
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Page/Page column 40
(2008/06/13)
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