- Aminoacetyl moiety as a potential surrogate for diacylhydrazine group of SC-51089, a potent PGE2 antagonist, and its analogs.
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8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocytes, SC-51089, which contains a diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure-activity relationships within these series.
- Hallinan, E. Ann,Hagen, Timothy J.,Tsymbalov, Sofya,Husa, Robert K.,Lee, Albert C.,et al.
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Read Online
- Short & expedient synthesis of pyridine containing dihydrochalcone 1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propan-1-one: A non-nutritive artificial sweetener
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An efficient synthesis of the artificial sweetener 1-(2-hydroxyphenyl)-3-(pyridin-4- yl)propan-1-one employing Fries Rearrangement as a key step in the construction of pyridine containing dihydrochalcone is reported. A novel approach for the synthesis of
- Rafi, Shaik,Kandagatla, Bhaskar,Darapaneni, Balachennaiah,Oruganti, Srinivas
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p. 459 - 464
(2019/01/21)
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- NON-PEPTIDYL, POTENT, AND SELECTIVE MU OPIOID RECEPTOR ANTAGONISTS
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Selective, non-peptide antagonists of the ma opioid receptor { MOR) and methods of their use are provided. The antagonists may be used, for example, to identify MOR agonists in competitive binding assays, and to treat conditions related to addiction in which MOR is involved, e.g. heroin, prescription drug and alcohol addiction.
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Page/Page column 61
(2010/08/08)
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- CHEMOKINE RECEPTOR BINDING COMPOUNDS
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The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. Thesd compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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- PYRAZOLONAPHTHYRIDINE DERIVATIVE
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The target is to provide PDE IV inhibitors which have a highly potent anti-asthmatic and/or COPD-prophylactic/therapeutic profile with unexpectedly excellent safety. A compound of the formula (1): wherein A is phenyl, pyridyl, 1-oxypyridyl, or thienyl, which may be unsubstituted or optionally substituted with one or more members selected from the group consisting of hydroxyl, halogen, cyano, nitro, lower alkyl, lower alkoxy, lower alkylcarbonyloxy, amino, carboxyl, lower alkoxycarbonyl, carboxy-lower alkylene, lower alkoxycarbonyl-lower alkylene, lower alkylsulfonyl, lower alkylsulfonylamino, and ureido; R1 is a group selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, nitro, lower alkoxy, amino, carboxyl, and lower alkoxycarbonyl; R2 is hydrogen or lower alkyl; and m is an integer of 1 to 3; or a pharmaceutically acceptable salt thereof, possesses highly excellent PDE IV-specific inhibitory actions and is useful as an anti-asthmatic drug and/or a prophylactic/therapeutic drug for COPD with high safety.
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Page/Page column 19-20
(2008/06/13)
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- 4-[(4-(CARBOXYETHYL) PIPERIDINYL) METHYL] PYRROLIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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3-Substituted pyrrolidines having a 4-carboxypiperidinylmethyl substituent on the 4-position of the ring are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.
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- Direct synthesis of 3-arylpropionic acids by tetraphosphine/palladium catalysed Heck reactions of aryl halides with acrolein ethylene acetal
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Through the use of [PdCl(C3H5)]2/Cis,cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters was observed. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides. Graphical Abstract.
- Lemhadri, Mhamed,Doucet, Henri,Santelli, Maurice
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p. 11533 - 11540
(2007/10/03)
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- New broad-spectrum parenteral cephalosporins exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Part 3: 7β-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2- ethoxyiminoacetamido] cephalosporins beari
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Among the prepared C-3′ substituted-pyridinium cephalosporins, a series of 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido] cephalosporins bearing 4-[3-(aminoalkyl)-ureido]-1-pyridinium at C-3′ showed highly potent antibacterial activity agai
- Yoshizawa, Hidenori,Kubota, Tadatoshi,Itani, Hikaru,Minami, Kyoji,Miwa, Hideaki,Nishitani, Yasuhiro
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p. 4221 - 4231
(2007/10/03)
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- Nα-Imidazolylalkyl and Pyridylalkyl Derivatives of Histaprodifen: Synthesis and in Vitro Evaluation of Highly Potent Histamine H1-Receptor Agonists
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A novel series of Nα-imidazolylalkyl and pyridylalkyl derivatives of histaprodifen (6, 2-[2-(3,3-diphenylpropyl)imidazol-4-yl]ethanamine) was synthesized and evaluated as histamine H1-receptor agonists. The title compounds displayed partial agonism at contractile H1-receptors of guinea pig ileum and were at least equipotent with histamine. Agonist effects of the new derivatives were susceptible to blockade by the H1-receptor antagonist mepyramine (2-100 nM). In the imidazole series, suprahistaprodifen (51, [2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethyl]-[2-(1H-imidazol-4-yl) ethyl]amine, Nα-2-[(1H-imidazol-4-yl)ethyl]histaprodifen) showed the highest H1-receptor agonist potency ever reported in the literature (pEC50 8.26, efficacy Emax 96%). Elongation of the alkyl spacer from ethyl to butyl decreased activity from 3630% (ethyl, 51) to 163% (butyl, 53) of histamine potency. The exchange of the terminal imidazole nucleus for a pyridine ring resulted in compounds with comparably high potency. A decrease in agonist potency and efficacy was observed when the attachment of the alkyl spacer was consecutively changed from the ortho to the meta and the para position, respectively, of the pyridine ring. The pyridine series that contained a butyl chain possessed the highest potency and affinity. Nα-[4-(2-pyridyl)butyl]histaprodifen (56) emerged as a strong partial agonist, being almost equipotent with 51 (pEC50 8.16, E max 89%). Compounds 51 and 56 also showed potent partial agonism at contractile H1 receptors in guinea pig aorta and potently activated H1-receptor-mediated endothelium-dependent relaxation in the rat aorta. Compounds 51-65 displayed low to moderate affinity at H2, H3, and M3 receptors in functional models of guinea pig. Collectively, Nα-imidazolylalkyl- and Nα -pyridylalkyl-substituted histaprodifens represent a novel class of potent H1-receptor agonists. These compounds may be useful to define the (patho)physiological role of the H1-receptor and refine molecular models of H1-receptor activation.
- Menghin, Sonja,Pertz, Heinz H.,Kramer, Kai,Seifert, Roland,Schunack, Walter,Elz, Sigurd
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p. 5458 - 5470
(2007/10/03)
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- Gamma-hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides and uses thereof
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γ-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamide compounds are inhibitors of HIV protease and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. These compounds are effective against HIV viral mutants which are resistant to HIV protease inhibitors currently used for treating AIDS and HIV infection.
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Page/Page column 131-132
(2010/01/31)
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- Amino substituted dibenzothiophene derivatives for the treatment of disorders mediated by np y5 receptor
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Compounds of formula (I): wherein: X is a group of formula (A) or (B): and R1, R2, R3, R4, n, x, y and z are as defined within are described. Processes for their preparation and their use in the treatment of disorders mediated by the neuropeptide Y5 receptor in a warm-blooded animal, such as a human being are also described.
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- Certain 1-hydroxyethane, 1,1-di-phosphonic acid derivatives useful in treating calcium metabolism disturbances
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The present invention provides diphosphonates of the general formula: STR1 wherein Het is an imidazole, oxazole, isoxazole, thiazole, pyridine, 1,2,3-triazole, 1,2,4-triazole or benzimidazole radical, which is optionally substituted by alkyl, alkoxy, halogen, hydroxyl, carboxyl, an amino group optionally substituted by alkyl or alkanoyl radicals or a benzyl radical optionally substituted by alkyl, nitro, amino or aminoalkyl, A is a straight-chained or branched, saturated or unsaturated hydrocarbon chain containing 2 to 8 carbon atoms, X is a hydrogen atom, optionally substituted by alkanoyl, or an amino group optionally substituted by alkyl or alkanoyl radicals and R is a hydrogen atom or an alkyl radical; and the pharmacologically acceptable salts thereof. The present invention also provides processes for the preparation of these diphosphonates and pharmaceutical compositions containing them.
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