- 1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to 1,3,4-oxadiazole derivative compounds having a histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, a use thereof in preparation of a medicament, a pharmaceutical composition comprising the same, a therapeutic method using the composition, and a method for preparing the same, and the 1,3,4-oxadiazole derivative compounds are represented by a following chemical formula (I).
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Page/Page column 643-644
(2020/12/11)
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- PHARMACEUTICAL COMPOUNDS
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Benzimidazole derivatives of formula (I): wherein: R1 is -(CH2)m-R4 or R2 is halo, -(CH2)m-NH2 or -(CH2)n-C(=NH)-NH2; R3 is H or F; R4 is -NH-(CH2)2-(NH)r-R5, -NH-(CHR5R6) or a group of the following formula (A): (A) W is -(CH2)m-, -CH2-O-CH2-, -CH2-S-CH2-, -(CH2)r-S(O)2-CH2- or -(CH2)r-NR5-CH2-; m is an integer of 1 to 3; n is 1 or 2; p is 1 and V is CH; or p is O and V is N; q is 0 or 1; r is 0 or 1; R5 is H, -S02Me, -SO2Et, -SO2CF3, -COMe, -CONMe2, - CONH2 or -CH2CH2SO2Me; R6 is H or C1-C6 alkyl; and R7 is -SO2Me, -SO2Et, -SO2CF3, -COMe, -CONMe2, - CONH2 or -CH2CH2SO2Me; and the pharmaceutically acceptable salts thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection.
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Page/Page column 18; 19
(2019/02/06)
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- PHARMACEUTICAL COMPOUNDS
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Benzimidazole derivatives of formula (I): (Formula (I)) wherein: R1is -(CH2)m-R7, (Formula (II)) or (Formula (III)); R2 is H, halo, -(CH2)m-NH2, -(CH2)n-C(=NH)-NH2 or -(CH2)n-NH-(CH2)m-NHR9; R3 is H, F or Cl; each of R4, R5 and R6 is independently H or F; R7 is C1-C6 alkyl, CF3, -SO2R11, -NH-(CH2)2-(NH)r-R8, -NH-CH(R8R9) or a group of the following formula (A): (Formula (A)): W is -(CH2)m-, -CH2-O-CH2-, -CH2-S-CH2-, -(CH2)r-S(O)2-CH2-or -(CH2)r-NR8-CH2-; m is an integer of 1 to 3; n is 1 or 2; p is 1 and V is CH; or p is 0 and V is N; q is 0 or 1; r is 0 or 1; R8 is H, -SO2R11,-SO2CF3, -COR11, -C(O)OR11, -CON(R9)2 or -(CH2)nSO2R11; R9 is H or C1-C6 alkyl, each R9 being the same or different when two are present; R10 is -SO2R11, -SO2CF3, -COR11, -CON(R9)2 or -(CH2)nSO2R11; and R11 is C1-C6 alkyl; and the pharmaceutically acceptable salts thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection.
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Page/Page column 19; 20
(2019/07/13)
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- Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias
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While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/βarr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.
- Kennedy, Nicole M.,Schmid, Cullen L.,Ross, Nicolette C.,Lovell, Kimberly M.,Yue, Zhizhou,Chen, Yen Ting,Cameron, Michael D.,Bohn, Laura M.,Bannister, Thomas D.
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p. 8895 - 8907
(2018/10/05)
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- Concise and simple synthesis of M1 allosteric agonist TBPB
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A concise and simple synthesis of M1 allosteric agonist 1-(1′-(2-methylbenzyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d] imidazol-2(3H)-one (TBPB) using economical and commercially available orthophenylenediamine (O-PDA) and Boc piperidone has been described. The disclosed scheme allows synthesizing more analogs that were otherwise difficult to prepare with the original method. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Rasheed, Mohammed Abdul,Shaik, Nagul Meera,Nirogi, Ramakrishna
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p. 1796 - 1801
(2013/05/21)
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