- Identification of N-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents
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A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC 0.016-0.125 μg/mL). Compound D6 displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.
- Li, Linhu,Lv, Kai,Yang, Yupeng,Sun, Jingquan,Tao, Zeyu,Wang, Apeng,Wang, Bin,Wang, Hongjian,Geng, Yunhe,Liu, Mingliang,Guo, Huiyuan,Lu, Yu
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p. 741 - 745
(2018/07/05)
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- A fragment merging approach towards the development of small molecule inhibitors of Mycobacterium tuberculosis EthR for use as ethionamide boosters
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With the ever-increasing instances of resistance to frontline TB drugs there is the need to develop novel strategies to fight the worldwide TB epidemic. Boosting the effect of the existing second-line antibiotic ethionamide by inhibiting the mycobacterial
- Nikiforov, Petar O.,Surade, Sachin,Blaszczyk, Michal,Delorme, Vincent,Brodin, Priscille,Baulard, Alain R.,Blundell, Tom L.,Abell, Chris
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p. 2318 - 2326
(2016/03/01)
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- Lead optimization of a novel series of imidazo[1,2-a]pyridine amides leading to a clinical candidate (Q203) as a multi- and extensively-drug- resistant anti-tuberculosis agent
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A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.
- Kang, Sunhee,Kim, Ryang Yeo,Seo, Min Jung,Lee, Saeyeon,Kim, Young Mi,Seo, Mooyoung,Seo, Jeong Jea,Ko, Yoonae,Choi, Inhee,Jang, Jichan,Nam, Jiyoun,Park, Seijin,Kang, Hwankyu,Kim, Hyung Jun,Kim, Jungjun,Ahn, Sujin,Pethe, Kevin,Nam, Kiyean,No, Zaesung,Kim, Jaeseung
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p. 5293 - 5305
(2014/07/08)
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- Anti-Inflammation Compounds
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The present invention refers to: a compound having the general formula (I), wherein n is 0, 1, 2 or; m is 0, 1, 2 or 3; o is 0, 1, 2 or 3; W, X, Y and Z are independently selected from CH, N or N-oxide; A is NR4, C═O, C═S, OP(O)(O), P═O, CH2, or a heteroarly selected from the group consisting of (a), (b), (c), (d), (e), (f), (g); V is C═O, O, S, CH2, or NR5; as well as its use in treating inflammatory diseases such as asthma, COPD, inflammation post infection, arthritis, atherosclerosis, pain and dermatitis.
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- "TRPV1 VANILLOID RECEPTOR ANTAGONISTS WITH A BICYCLIC PORTION"
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The invention discloses compounds of formula I wherein Y is a group of formula A, B, C, D, or E: and W, Q, n, R1, R2, R3, U1-U5, J and K have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active
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- TRPV1 vanilloid receptor antagonists with a bicyclic portion
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The invention discloses compounds of formula I wherein Y s selected from a group of formula and W, Q, n, R1, R2, R3, U1-U5 have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active ingredients of pharmaceutical compositions for the treatment of pain and other conditions ameliorated by the inhibition of the vanilloid receptor TRPV1. 1.
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- ANTI-INFECTIVE COMPOUNDS
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The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
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- THERAPEUTIC MACROLIDE COMPOUNDS AND THEIR USE
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain macrolide compounds (for convenience, collectively referred to herein as "MC compounds"), which, inter alia, are useful in treatment of cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to treat proliferative conditions such as cancer, and in the treatment of diseases and conditions that are mediated by the regulation (e.g. inhibition) of cell proliferation, optionally in combination with another agent.
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Page/Page column 90, 92
(2010/06/17)
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- In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists
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The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino) benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.
- Perner, Richard J.,DiDomenico, Stanley,Koenig, John R.,Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Drizin, Irene,Guo, Zhu Zheng,Turner, Sean C.,Jinkerson, Tammie,Brown, Brian S.,Keddy, Ryan G.,Lukin, Kurill,McDonald, Heath A.,Honore, Prisca,Mikusa, Joe,Marsh, Kennan C.,Wetter, Jill M.,St. George, Karen,Jarvis, Michael F.,Faltynek, Connie R.,Lee, Chih-Hung
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p. 3651 - 3660
(2008/02/12)
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