The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
K F Austen - One of the best experts on this subject based on the ideXlab platform.
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the paul kallos memorial lecture from Slow Reacting Substance of anaphylaxis to leukotriene c4 synthase
International Archives of Allergy and Immunology, 1995Co-Authors: K F AustenAbstract:The hypothesis of 35 years ago that SlowReacting Substance of anaphylaxis would prove to be a pathobiologic mediator of reversible airway disease in the human has been validated. The multidisciplinary approach required to achieve this goal has been particularly prominent and consistent for the entire period in the program described in this presentation.
Masaaki Matsuo - One of the best experts on this subject based on the ideXlab platform.
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synthesis and structure activity relationships of antiallergic n 4 4 1h indol 3 yl piperidinoalkyl 2 thiazolyl alkanamides possessing both antihistaminic and anti Slow Reacting Substance srs activities
ChemInform, 2010Co-Authors: Shinji Shigenaga, Takashi Manabe, Hiroshi Matsuda, Takashi Fujii, Masaaki MatsuoAbstract:A series of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamide derivatives were synthesized and tested for in vivo antianaphylactic activity and in vitro anti Slow-Reacting Substance (SRS) activity. Among the compounds synthesized, N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]propanamide (7) was the best balanced compound (antianaphylactic activity, ED50=0.92mg/kg p.o.; anti-SRS activity, IC50=0.89μg/ml). Regarding the biological activities of 7, we ascribe the antianaphylactic activity to its potent antihistaminic activity and the anti SRS activity to the inhibition of 5-lipoxygenase.
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2e 4e n 4 1h indol 3 yl piperidin 1 yl alkyl 5 substituted phenyl 2 4 pentadienamides as antiallergic agents with antihistaminic and anti Slow Reacting Substance srs activities
Archiv Der Pharmazie, 1996Co-Authors: Shinji Shigenaga, Takashi Manabe, Hiroshi Matsuda, Takashi Fujii, Masaaki MatsuoAbstract:As an extension of our study aiming to discover a novel compound with dual activities against histamine and Slow-Reacting Substance (SRS), we synthesized two types of indolylpiperidine derivatives, 3 and 4-20. Testing for in vivo antianaphylactic activity and for in vitro anti-SRS activity revealed that (2E,4E)-5-(3,5-dimethoxy-4-hydroxyphenyl)-N-(2-(4-(1H-indol-3-yl)+ ++piperidin-1- yl)ethyl)-2,4-pentadienamide (11) exhibited potent dual activities with ED50 = 0.89 mg/kg and IC50 = 1.43 microM, respectively. However, the plasma concentration of unchanged 11 was very low when administered orally in guinea pigs. This result can be explained by fast formation of a glucuronic acid conjugate.
Paul M Obyrne - One of the best experts on this subject based on the ideXlab platform.
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treatment of asthma with drugs modifying the leukotriene pathway
The New England Journal of Medicine, 1999Co-Authors: Jeffrey M Drazen, Elliot Israel, Paul M ObyrneAbstract:In 1979 and 1980, the chemical structures of the material previously known as Slow-Reacting Substance of anaphylaxis were elucidated as 5(S)- hydroxy- 6(R)-glutathionyl- 7,9-trans-11,14- cis - eico- satetraenoic acid1 and its cysteinyl-glycyl and cysteinyl congener (also known as leukotrienes C4, D4, and E4, respectively). These molecules were so named because the parent molecule was originally isolated from leukocytes, and its carbon backbone contained three double bonds in series, which constitutes a triene. This structural information provided the key to the oxidative pathway of lipid metabolism known as the 5-lipoxygenase pathway. One of . . .
Shinji Shigenaga - One of the best experts on this subject based on the ideXlab platform.
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synthesis and structure activity relationships of antiallergic n 4 4 1h indol 3 yl piperidinoalkyl 2 thiazolyl alkanamides possessing both antihistaminic and anti Slow Reacting Substance srs activities
ChemInform, 2010Co-Authors: Shinji Shigenaga, Takashi Manabe, Hiroshi Matsuda, Takashi Fujii, Masaaki MatsuoAbstract:A series of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamide derivatives were synthesized and tested for in vivo antianaphylactic activity and in vitro anti Slow-Reacting Substance (SRS) activity. Among the compounds synthesized, N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]propanamide (7) was the best balanced compound (antianaphylactic activity, ED50=0.92mg/kg p.o.; anti-SRS activity, IC50=0.89μg/ml). Regarding the biological activities of 7, we ascribe the antianaphylactic activity to its potent antihistaminic activity and the anti SRS activity to the inhibition of 5-lipoxygenase.
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2e 4e n 4 1h indol 3 yl piperidin 1 yl alkyl 5 substituted phenyl 2 4 pentadienamides as antiallergic agents with antihistaminic and anti Slow Reacting Substance srs activities
Archiv Der Pharmazie, 1996Co-Authors: Shinji Shigenaga, Takashi Manabe, Hiroshi Matsuda, Takashi Fujii, Masaaki MatsuoAbstract:As an extension of our study aiming to discover a novel compound with dual activities against histamine and Slow-Reacting Substance (SRS), we synthesized two types of indolylpiperidine derivatives, 3 and 4-20. Testing for in vivo antianaphylactic activity and for in vitro anti-SRS activity revealed that (2E,4E)-5-(3,5-dimethoxy-4-hydroxyphenyl)-N-(2-(4-(1H-indol-3-yl)+ ++piperidin-1- yl)ethyl)-2,4-pentadienamide (11) exhibited potent dual activities with ED50 = 0.89 mg/kg and IC50 = 1.43 microM, respectively. However, the plasma concentration of unchanged 11 was very low when administered orally in guinea pigs. This result can be explained by fast formation of a glucuronic acid conjugate.
Keigo Nishino - One of the best experts on this subject based on the ideXlab platform.
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Effect of Ibudilast, a Novel Antiasthmatic Agent, on Anaphylactic Bronchoconstriction: Predominant Involvement of Endogenous Slow Reacting Substance of Anaphylaxis
International Archives of Allergy and Immunology, 1993Co-Authors: Mitsuo Ohashi, Takashi Uno, Keigo NishinoAbstract:The effect of ibudilast on anaphylactic bronchoconstriction was studied in guinea pigs sensitized actively with ovalbumin (OA). Animals were treated with indomethacin, tripelennamine and propranolol prior to the antigen challenge. Anaphylactic bronchoconstriction was prevented by ibudilast (1–4 mg/kg i.v. and 5–20 mg/kg p.o.) dose-dependently. FPL55712 and phenidone were also effective. Even when administered at the maximum development of bronchoconstriction, ibudilast (0.5 and 2 mg/kg i.v.) and FPL 55712 caused significant reduction of the increased airway tone, while phenidone did not. Ibudilast (1–4 mg/kg i.v.) and FPL55712 inhibited leukotriene D4-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol. Ibudilast (1.6 and 4 mg/kg i.v.) inhibited platelet-activating-factor (PAF)-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol, however, FPL 55712 inhibited PAF-induced airway responses only at a high dose such as 10 mg/kg i.v. Ibudilast (4 mg/kg i.v.) did not inhibit acetylcholine-induced airway response. Ibudilast showed inhibition of the release of Slow-Reacting Substance of anaphylaxis (SRS-A) from guinea pig chopped lung sensitized with OA, which was significantly diminished by indomethacin. The drug little affected the activity of phospholipase A2 and 5-lipoxygenase in guinea pig polymorphonuclear leukocytes. These results indicate that ibudilast inhibits anaphylactic bronchoconstriction which is considered to be largely mediated by endogenously released SRS-A. The inhibitory effect of ibudilast on anaphylactic bronchoconstriction in the presence of indomethacin is considered to be exerted through its antagonism to SRS-A.