Arachidonic acid plays a central role in a biological control system where such oxygenated derivatives as prostaglandins, thromboxanes, and leukotrienes are mediators. The leukotrienes are formed by transformation of arachidonic acid into an unstable epoxide intermediate, leukotriene A4, which can be converted enzymatically by hydration to leukotriene B4, and by addition of glutathione to leukotriene C4. This last compound is metabolized to leukotrienes D4 and E4 by successive elimination of a gamma-glutamyl residue and glycine. Slow-reacting substance of anaphylaxis consists of leukotrienes C4, D4, and E4. The cysteinyl-containing leukotrienes are potent bronchoconstrictors, increase vascular permeability in postcapillary venules, and stimulate mucus secretion. Leukotriene B4 causes adhesion and chemotactic movement of leukocytes and stimulates aggregation, enzyme release, and generation of superoxide in neutrophils. Leukotrienes C4, D4, and E4, which are released from the lung tissue of asthmatic subjects exposed to specific allergens, seem to play a pathophysiological role in immediate hypersensitivity reactions. These leukotrienes, as well as leukotriene B4, have pro-inflammatory effects.

https://science.sciencemag.org/content/sci/220/4597/568.full.pdf

Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation

Catalytic amounts of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) are used in combination with [bis(acetoxy)iodo]benzene (BAIB) as a stoichiometric oxidant in the conversion of primary and secondary alcohols to carbonyl compounds. This procedure works efficiently at room temperature in almost all common solvents and neat in some cases. This process exhibits a very high degree of selectivity for the oxidation of primary alcohols to aldehydes, without any noticeable overoxidation to carboxyl compounds, and a high chemoselectivity in the presence of either secondary alcohols or of other oxidizable moieties. This procedure allows an easy, convenient, high-yielding method for the oxidation of alcohols starting from commercially available compounds.

A Versatile and Highly Selective Hypervalent Iodine (III)/2,2,6,6-Tetramethyl-1-piperidinyloxyl-Mediated Oxidation of Alcohols to Carbonyl Compounds

Objective: To review the biochemistry and biological activities of leukotrienes, focusing on their role in the mediation of inflammatory diseases. Data Sources: MEDLINE (1966-1994), EMBASE (Excerpt...

The Role of Leukotrienes in Inflammation

Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

Vanilloid receptor ligands and their use in treatments

Recent advances in the preparation and synthetic applications of oxiranes

(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS-411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.

New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships

Total synthesis of (.+-.)-5,6-oxido-7,9-trans,11,14-cis-eicosapentaenoic acid, a possible precursor of SRSA

TITLE OF THE INVENTION (FUSED) B E N Z (THIO) A M I D E S A B S T R A C T A novel (fused) benz(thio)amides of the general formula: (I) (wherein, symbol A represents a single bond or a group of methylene, ethylene, trimethylene, tetramethylene, vinylene, propenylene, butenylene, butadienylene or ethynylene group optionally being substituted by one, two or three of straight or branched alkyl group(s) of from 1 to 10 carbon atom(s) and/or phenyl group(s). Symbol B represents (i) a carbocyclic ring of from 4 to 8 members being unreplaced or replaced one, two or three of optional carbon atom(s) by oxygen, nitrogen and/or sulphur atom(s). (The ring may optionally be substituted by group(s) of oxo, thioxo and/or hydroxy group(s).) or (ii) a divalent group of formula: or Symbol T represents an oxygen atom or a sulphur atom. R1 represents a group of general formula: (i) (ii) or (iii) or (iv) a straight or branched alkyl, alkenyl or alkynyl group or from 1 to 20 carbon atom(s). (wherein R5 and R6 independently represent a hydrogen atom or a halogen atom or a straight or branched alkyl, alkenyl or alkynyl group of from 1 to 20 carbon atom(s) being unreplaced or replaced one, two,three, four or five of optional carbon atom(s) by oxygen atom(s), sulphur atom(s), halogen atom(s), nitrogen atom(s), benzene ring(s), thiophene ring(s), naphthalene ring(s), carbocyclic ring(s) or from 4 to 7 carbon atom(s), carbonyl group(s), carbonyloxy group(s), hydroxy group(s), carboxy group(s), azido group(s) and/or nitro croup(s)). R2 represents a hydrogen atom or a straight or branched alkyl group of from 1 to 6 carbon atom(s) R3 represents a hydrogen atom, a halogen atom, a hydroxy group, a nitro group, a group of general formula: -COOR7 (wherein R7 represents a hydrogen atom or a straight or branched alkyl group of from 1 to 6 carbon atom(s).) or a straight or branched alkyl, alkoxy or alkylthio group of from 1 to 6 carbon atom(s). R represents (i) when symbol B represents a closed ring, a group of general formula: or (wherein symbol U represents an oxygen atom or a sulphur atom. R8 represents a hydrogen atom or a straight or branched alkyl group of from 1 to 6 carbon atom(s). n and m represent an integer of from 1 to 10, respectively, p and q represent zero or an integer of from 1 to 10, respectively.) or (ii) when symbol B do not represent a ring, a group of general formula: or (wherein R8, p and q represent the same meaning as depicted hereinbefore. With the proviso that, when the symbol Brepresents a group of formula: p does not represent zero.) With the proviso that, following compounds are excluded, i.e. compounds of general formula: (I') (wherein the symbol A' is 2 vinylene or ethylene group optionally being substituted by straight or branched alkyl group(s) of from 1 to 4 carbon atom(s), R4' is the general formula: -(CH2)n-COOR8 (wherein all the symbols axe the same meaning as depicted hereinbefore.) and R1' is (i) a group of the general formula: (wherein R5' and R6' are hydrogen atom(s), hydroxy group(s), halogen atom(s), straight or branched alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy or acyloxy group(s) of from 1 to 4 carbon atom(s) or cycloalkyl group(s) of from 3 to 6 carbon atom(s), independently.) or (ii) a group of the general formula: (wherein R5' and R6' are the same meaning as depicted hereinbefore.)) or non-toxic salts thereof possess an antagonistic activity on leukotrienes (SRS), inhibitory activity on 5.alpha.-reductase, on phosphtolipase and on aldose reductase and are therefore useful for the prevention and/or treatment for diseases induced by leukotrienes, 5.alpha.-reductase, phospholipase and aldose reductase in mammals, especially human beings.

fused)benz(thio)amides

A benzoylaminophenoxybutanoic acid derivative of general formula: ##STR1## [wherein R1 represents hydrogen atom or alkyl group of from 1 to 4 carbon atoms(s), A represents oxygen atom, sulfur atom or sulfinyl (SO) group, two R1 s represents methyl groups or chlorine atoms at the same time or cyclopentane, cyclohexane or benzene ring together with the carbon atoms of benzene ring each attaching, R2 represents a group of general formula: ##STR2## {wherein B represents oxygen atom, sulfur atom or a group of general formula: NR11 (wherein R11 represents hydrogen atom or alkyl group of from 1 to 4 carbon atom(s)), R3, R4, R5, R6, R7 and R8 represent, independently, hydrogen atom, alkyl group of from 1 to 4 carbon atom(s) halogen atom, trifluoromethyl group or cyclobutylmethyl group, m represents 0 or 1, n represents an integer of from 1 to 5, and R9 and R10 represent, independently, hydrogen atom, alkyl group of from 1 to 5 carbon atom(s) or a group of general formula: ##STR3## (wherein R12, R13, R14 and R15 represent, independently, hydrogen atom, alkyl group of from 1 to 4 carbon atom(s), halogen atom, trifluoromethyl group or cyclobutylmethyl group, and l represents an integer of from 1 to 4). With the proviso that R9 and R10 do not represent hydrogen atoms at the same time}] and non-toxic salts thereof possess an inhibitory activity on 5α-reductase, and therefore be useful for treating and/or preventing agent for alopecia, acnes or prostatic hypertrophy.

Yoshinobu Arai

Papers

New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships

Total synthesis of (.+-.)-5,6-oxido-7,9-trans,11,14-cis-eicosapentaenoic acid, a possible precursor of SRSA

fused)benz(thio)amides

Benzoylaminophenoxybutanoic acid derivatives

Synthesis of clavulones (claviridenones)