139140-55-9Relevant academic research and scientific papers
Synthesis and evaluation of simplified functionalized bongkrekic acid analogs
Fujita, Satoshi,Suyama, Masaki,Matsumoto, Kenji,Yamamoto, Atsushi,Yamamoto, Takenori,Hiroshima, Yuka,Iwata, Takayuki,Kano, Arihiro,Shinohara, Yasuo,Shindo, Mitsuru
, p. 962 - 969 (2018)
Bongkrekic acid (BKA) is a strong inhibitor of adenine nucleotide translocase (ANT), inducing inhibition of adenosine triphosphate synthesis. We designed and synthesized simplified benzene-ring-containing BKA analogs. The key reaction is the one-pot double Sonogashira reaction, which forms the main skeleton. The analogs were efficiently synthesized in 8–10 longest linear sequence steps. This synthetic method can be applied for the preparation of other analogs having different combinations of carbon chain lengths. Furthermore, the allyloxy group on the benzene ring can be easily replaced by other functional groups. Our preliminary biological evaluation based on mitochondrial inhibitory effects revealed the high potency of the analogs bearing the same carbon chain length as that of BKA. In particular, the prefunctionalized analogs are potential ANT inhibitors.
Pyridine compounds for treating leukotriene-related diseases
-
, (2008/06/13)
STR1 This invention relates to compounds of formula (I) which are useful as leukotriene antagonists.
(E)-3-[[[[6-(2-Carboxyethenyl)-5-[[8-(4-methoxyphenyl)octyl]oxy]-2- pyridinyl]-methyl]thio]methyl]benzoic acid and related compounds: High affinity leukotriene B4 receptor antagonists
Daines,Chambers,Eggleston,Foley,Griswold,Haltiwanger,Jakas,Kingsbury,Martin,Pendrak,Schmidt,Tzimas,Sarau
, p. 3327 - 3336 (2007/10/02)
(E)-3-[[[[6-(2-Carboxyethenyl)-5-[[8-(4-methoxyphenyl)octyl]oxy]-2- pyridinyl]-methyl]thio]methyl]benzoic acid (11, SB 201993) is a novel, potent LTB4 receptor antagonist. Compound 11 arose from a structure-activity study of a series of trisubstituted pyridines that demonstrated LTB4 receptor antagonist activity. The placement of an additional methylene unit in the sulfur containing chain linking the pyridine and benzoic acid moieties of lead compound 8 (K(i) = 80 nM) resulted in a greater than 10-fold increase in receptor affinity. Additionally, in this new series of compounds, the oxidation state of the sulfur was found to be critical to the activity, i.e., the sulfoxide and sulfone showed substantially lower affinity for the LTB4 receptor. Compound 11 competitively inhibits the binding of [3H]LTB4 to LTB4 receptors on human polymorphonuclear leukocutes with a K(i) of 7.1 nM and blocks both the LTB4-induced calcium mobilization and the LTB4-induced degranulation responses in these cells with IC50 values of 131 and 271 nM, respectively. Compound 11 demonstrated oral LTB4 antagonist activity as well as topical antiinflammatory activity in the mouse.
Trisubstituted Pyridine Leukotriene B4 Receptor Antagonists: Synthesis and Structure-Activity Relationships
Daines, Robert A.,Chambers, Pamela A.,Pendrak, Israil,Jakas, Dalia R.,Sarau, Henry M.,et al.
, p. 3321 - 3332 (2007/10/02)
A series of trisubstituted pyridines have been prepared that exhibit in vitro leukotriene B4 (LTB4, 1) receptor antagonist activity.Previous disubstituted pyridines from these labs showed high affinity for the LTB4 receptor but demonstrated agonist activity in functional assays (e.g., 2, Ki = 1 nM).Compound 4, the initial lead compound of this new series, showed only modest affinity by comparison (Ki = 282 nM); however, 4 was a receptor antagonist with no demonstrable agonist activity up to 10 μM.Subsequent modifications of the lipid tail and aryl head group region led to the discovery of aniline 50 (SB 201146).This compound, also free of agonist activity, possesses high affinity for the LTB4 receptor (Ki = 4.7 nM).
