- MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
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Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
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Paragraph 00632; 00863
(2018/09/12)
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- New azoles with potent antifungal activity: Design, synthesis and molecular docking
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In response to the urgent need for novel antifungal agents with improved activity and broader spectrum, computer modeling was used to rational design novel antifungal azoles. On the basis of the active site of lanosterol 14α-demethylase from Candida albicans (CACYP51), a series of new azoles with substituted-phenoxypropyl piperazine side chains were rational designed and synthesized. In vitro antifungal activity assay indicates that the new azoles show good activity against most of the tested pathogenic fungi. Interestingly, the designed compounds are also active against an azole-resistant clinical strain. Compared to fluconazole and itraconazole, several compounds (such as 12i, 12j and 12n) show higher antifungal activity and broader spectrum, which are promising leads for the development of novel antifungal agents.
- Che, Xiaoying,Sheng, Chunquan,Wang, Wenya,Cao, Yongbing,Xu, Yulan,Ji, Haitao,Dong, Guoqiang,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
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scheme or table
p. 4218 - 4226
(2009/12/09)
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- LTA4H modulators and uses thereof
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Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation.
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Page/Page column 28
(2008/12/07)
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- Studies towards the conception of new selective PPARβ/δ ligands
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In order to define new PPARβ/δ ligands, SAR study on the selective PPARβ/δ activator L-165,041 led to the identification of one key functional group for selective PPARβ/δ activation. Furthermore, taking advantage of SAR studies done elsewhere on the most selective PPARβ/δ ligand GW501516, the conception of new ligands showing good affinity for PPARβ/δ is reported. Finally, synthesis and biological evaluation of pyridine analogues have shown the benefical effect of the pyridine ring on the PPARβ/δ subtype selectivity.
- Ekambome Bassene, Carine,Suzenet, Franck,Hennuyer, Nathalie,Staels, Bart,Caignard, Daniel-Henri,Dacquet, Catherine,Renard, Pierre,Guillaumet, Gerald
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p. 4528 - 4532
(2007/10/03)
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- Phenyl and pyridyl LTA4H modulators
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Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and inflammatory conditions.
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Page/Page column 22
(2010/11/24)
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- BENZIMIDAZOLE, BENZTHIAZOLE AND BENZOXAZOLE DERIVATIVES AND THEIR USE AS LTA4H MODULATORS
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Leukotriene A4 hydrolase (LTA4H) inhibitors of formula I, compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation, wherein X is selected from the group consisting of NR5, O, and S, with R5 being one of the H and CH3; Y is selected from the group consisting of CH2 and O; R4 is selected from the group consisting of H, OCH3, Cl, F, Br, I, OH, NH2, CN, CF3.
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Page/Page column 76-77
(2010/02/10)
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- Synthesis and Pharmacological Evaluation of 1-Oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and Related Analogues as a New Class of Specific Bradycardic Agents Possessing If Channel Inhibitory Activity
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A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (± )-6,7-Dimethoxy-2-{1- [3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3, 4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against If currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of If currents (IC50 = 0.32 μM) in guinea pig pacemaker cells.
- Kubota, Hideki,Kakefuda, Akio,Watanabe, Toshihiro,Ishii, Noe,Wada, Koichi,Masuda, Noriyuki,Sakamoto, Shuichi,Tsukamoto, Shin-ichi
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p. 4728 - 4740
(2007/10/03)
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- SUBSTITUTED BENZOIC ACIDS, INHIBITORS OF PHOSPHOLIPASES A2
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The compounds of formula I are potent inhibitors of phospholipases A 2 (PLA 2 's) and are therefore useful in the treatment of diseases, such as psoriasis, inflammatory bowel disease, asthma, allergy, arthritis, dermatitis, gout, pulmonary disease, myocardial ischemia, and trauma induced inflammation, such as spinal cord injury.
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- Imidazolyl phenoxy compounds and method of use
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Imidazolyl phenoxy derivatives are provided as well as pharmaceutical compositions containing such derivatives. The compositions useful for lowering lipid activity in a subject and accordingly useful for reducing cholesterol and triglycerides.
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- Substituted (10H-phenothiazin-10-L)-propyl-1-piperazines
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Substituted (10H-phenothiazin-10-yl)propyl-1-piperazines of the formula STR1 wherein R1, R2, R3, A, X, m, n and s are as hereinafter set forth, are described. The compounds of formula I, which contain a piperazine moiety combined by an ether linkage to different phenolic moieties, are useful as orally active long lasting antipsychotic agents.
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- SUBSTITUTED PHENOXY-AMINOPROPANOL DERIVATIVES
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Phenoxy-aminopropanol derivatives of the formula STR1 wherein R is lower alkyl, X is oxygen or sulfur, n is the integer zero or 1, Y is methylene, ethylene or propylene or, when n is zero, Y can also be a group of the formula EQU1 , wherein the double-bond is trans and the carbon atom marked with an asterisk is linked to Z, and Z is a 5-membered aromatic heterocyclic ring which contains one or more nitrogen atoms as the sole hetero atom (s), said heterocyclic ring is linked to Y via a nitrogen atom, and may be substituted by halogen, lower alkyl, lower alkoxy, aryl, cyano or carboxamido, or on adjacent carbon atoms by a group of the formula STR2 and pharmaceutically acceptable acid addition salts thereof are described. A process for the preparation of the compound of formula I and pharmaceutical preparations containing them are also described. The aforementioned compounds and salts possess β-adrenergic blocking activity and antihypertensive activity.
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