- Histone Deacetylase Inhibitors for Enhancing Activity of Antifungal Agents
-
The present invention relates to compositions and methods to selectively treat fungal infection. More particularly, the invention relates to compounds, compositions thereof, and methods for selectively enhancing fungal sensitivity to antifungal compounds. The compositions of the invention are comprised of a combination of a histone deacetylase inhibitor, or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt, agricultural formulation, prodrug or complex thereof, and an antifungal agent, the histone deacetylase inhibitor being a compound of Formula (I):
- -
-
Paragraph 0352
(2014/04/03)
-
- Rhodium(I)-catalyzed intramolecular hydroacylation of 4,6-dienals: Novel synthesis of cycloheptenones
-
Rhodium(I)-catalyzed hydroacylation of 4,6-dienals was investigated. Hydroacylation of 4,6-dienals with a substituent at the C7 position produced cycloheptenone derivatives as the major products, while the cyclization of 4,6-dienals with no substituent at the terminus of the diene moiety preferentially gave cyclopentanone derivatives. The olefinic geometry of the diene moiety in 4,6-dienals also affected the reaction course, and the cyclization of substrates with an E-olefin at the C6 position produced cycloheptenone derivatives as the major products, while a cyclopentanone derivative was obtained from a substrate with a Z-olefin at the C6 position. Georg Thieme Verlag Stuttgart.
- Oonishi, Yoshihiro,Mori, Miwako,Sato, Yoshihiro
-
p. 2323 - 2336
(2008/02/13)
-
- Nucleosides and nucleotides. 107. 2-(cycloalkylalkynyl)adenosines: Adenosine A2 receptor agonists with potent antihypertensive effects
-
Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosine (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100 μg/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3 position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.
- Abiru,Miyashita,Watanabe,Yamaguchi,Machida,Matsuda
-
p. 2253 - 2260
(2007/10/02)
-
- Novel 6-alkyl and 6.8-dialkylbicyclo(4.2.0)octane derivatives
-
Compounds useful in treating or preventing gastrointestinal ulcers and in treating cardiovascular disorders such as thrombosis, hypertension and atherosclerosis are depicted in formulas (1), (2) and (3): STR1 wherein: A is --C C--, trans --HC=CH--, trans --CH=CHCH2 -- or --CH2 CH2 --; X is lower alkyl of 1-6 carbon atoms; Y is hydrogen, exo-(lower alkyl) or endo-(lower alkyl); n is an integer from 2-4; R1 is --CH2 OH, --CHO, --CO2 R or --CO2 H, and the olefin formed by the R1 (CH2)n CH= moiety is either (E) or (Z); R2 is hydrogen or methyl, or optionally --CH=CH2 when A is trans --CH=CHCH2 --; and R3 is linear or branched alkyl, alkenyl or alkynyl having 5-10 carbon atoms, STR2 --(CH2)m -phenyl or CH2 O-phenyl; in which each phenyl may be optionally substituted with lower alkyl, lower alkoxy, trifluoromethyl, or halogen. in which: a is an integer of 0, 1 or 2; b is an integer of 3-7; m is an integer of 0, 1 or 2; and R is STR3 wherein X' is STR4 in which each R4 is independently hydrogen or lower alkyl having 1-6 carbon atoms, or a pharmaceutically acceptable, non-toxic salt or ester thereof.
- -
-
-