- Design, synthesis and evaluation of MCH receptor 1 antagonists - Part I: Optimization of HTS hits towards an in vivo efficacious tool compound BI 414
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Abstract Despite recent approvals of anti-obesity drugs there is still a high therapeutic need for alternative options with higher efficacy in humans. As part of our MCH-R1 antagonist program for the treatment of obesity, a series of biphenylacetamide HTS
- Müller, Stephan G.,Heckel, Armin,Kley, J?rg T.,Lehmann, Thorsten,Lustenberger, Philipp,Oost, Thorsten,Roth, Gerald J.,Rudolf, Klaus,Arndt, Kirsten,Lenter, Martin,Lotz, Ralf R.H.,Maier, Gerd-Michael,Markert, Michael,Schindler, Marcus,Stenkamp, Dirk
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p. 3264 - 3269
(2015/07/08)
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- An in situ acidic carbon dioxide/glycol system for aerobic oxidative iodination of electron-rich aromatics catalyzed by Fe(NO3)3·9H2O
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An environmentally benign CO2/glycol reversible acidic system was developed for the iron(iii)-catalyzed aerobic oxidative iodination of electron-rich aromatics without the need for any conventional acid additive or organic solvent. Notably, moderate to high isolated yields (up to 97%) of the aryl iodides were attained with comparable regioselectivity when ferric nitrate nonahydrate was used as the catalyst with molecular iodine under 1 MPa of CO2.
- Ma, Ran,Huang, Cheng-Bin,Liu, An-Hua,Li, Xue-Dong,He, Liang-Nian
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p. 4308 - 4312
(2015/01/08)
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- The inhibition of monoamine oxidase by 8-(2-phenoxyethoxy)caffeine analogues
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Previous studies have documented that substituted 8-oxycaffeines act as inhibitors of human monoamine oxidase (MAO) B. A particularly potent inhibitor among the reported compounds was 8-(2-phenoxyethoxy)caffeine with an IC 50 value of 0.383M towards MAO-B. In an attempt to improve on the inhibition potency of this compound and to discover highly potent reversible MAO-B inhibitors, in the present study, a series of 8-(2-phenoxyethoxy)caffeine analogues containing various substituents on C4 of the phenoxy ring, were synthesized and evaluated as inhibitors of human MAO-A and -B. The results show that the 8-(2-phenoxyethoxy)caffeine analogues are selective and reversible MAO-B inhibitors with the most potent homologue, 8-{2-[4-(trifluoromethyl) phenoxy]ethoxy}caffeine, exhibiting an IC50 value of 0.061μM. These highly potent inhibitors are useful leads in the design of therapies for neurodegenerative disorders such as Parkinsons disease. Georg Thieme Verlag KG Stuttgart New York.
- Strydom,Bergh,Petzer
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p. 513 - 518
(2013/01/15)
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- Synthesis of new cores and their use in the preparation of polyester dendrimers
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Six dendrimer and dendron cores terminated by hydroxyl groups that are neither phenolic nor cleavable by hydrogenolysis have been prepared in a consistent one-pot manner from terminal allyl groups by reduction of the product of reductive ozonolysis. Some of the terminal allyl derivatives are new and others have been prepared by new methods. The well-known O-benzylidene derivative of 2,2′-bis(hydroxymethyl)propanoic acid was shown to be the cis-stereoisomer. A new AB3-type anhydride, tris(benzyloxymethyl) acetic anhydride has been prepared. It was demonstrated that these cores and dendrons could be assembled into first and second generation homo- and mixed polyester dendrimers.
- Twibanire, Jean-D'Amour K.,Al-Mughaid, Hussein,Grindley, T. Bruce
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experimental part
p. 9602 - 9609
(2011/01/03)
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- NEW PYRIDAZINE DERIVATIVES WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
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The present invention relates to compounds of general formula I wherein the groups and radicals B, W, X, Y, Z, R1, R2, have the meanings given in claim 1. Moreover the invention relates to pharmaceutical compositions containing at least one compound according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.
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Page/Page column 96
(2008/12/06)
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- Quick assembly of 1,4-diphenyltriazoles as probes targeting β-amyloid aggregates in Alzheimer's disease
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Accumulation of β-amyloid aggregates (Aβ) in the brain is linked to the pathogenesis of Alzheimer's disease (AD). We report a novel approach for producing 1,4-diphenyltriazoles as probes for targeting Aβ aggregates in the brain. The imaging probes, a seri
- Qu, Wenchao,Kung, Mei-Ping,Hou, Catherine,Oya, Shunichi,Kung, Hank F.
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p. 3380 - 3387
(2008/02/08)
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- NOVEL HETEROCYCLIC AMIDE DERIVATIVES HAVING DIHYDROOROTATE DEHYDROGENASE INHIBITING ACTIVITY
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Novel heterocyclic amide derivatives having pharmacological effects, that is, compounds represented by the general formula (1) or salts thereof: (1) wherein X1-X2 is S-CH2 or the like; R1 is alkyl or the like; p is 0 to 7; R2 is hydrogen, alkyl, or the like; R3 is hydrogen, alkyl, or the like; Y1-Y2 is CH=CH or the like; R4 is halogeno, alkyl, or the like; q is 0 to 4; and R5 is halogeno, hydrogen, alkyl, or the like.
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Page/Page column 60; 61
(2010/10/20)
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- Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds
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The present invention relates to alkyne compounds of general formula I wherein the groups and radicals A, B, W, X, Y, Z, R1 and R2 have the meanings given in claim 1. Moreover the invention relates to pharmaceutical compositions containing at least one alkyne according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity and diabetes.
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Page/Page column 34
(2010/02/14)
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- NOVEL ALKYNE COMPOUNDS WITH AN MCH-ANTAGONISTIC ACTION AND MEDICAMENTS CONTAINING SAID COMPOUNDS
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The invention relates to alkyne compounds of general formula (I), in which the groups and radicals A, B, W, X, Y, Z, R1 and R2 are defined as cited in claim 1. The invention also relates to medicaments containing at least one inventive alkyne. As a result of the antagonistic action against the MCH-receptor, the inventive medicaments are suitable for treating metabolic disorders and/or eating disorders, in particular adiposity and diabetes.
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Page/Page column 82
(2010/02/14)
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- NOVEL ALKYNE COMPOUNDS HAVING AN MCH ANTAGONISTIC EFFECT AND MEDICAMENTS CONTAINING THESE COMPOUNDS
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The invention relates to alkyne compounds of general formula (I), in which groups and residues A, B, W, X, Y, Z, R1 and R2 have the meanings as cited in Claim 1. The invention also relates to medicaments containing at least one inventive alkyne. The MCH receptor antagonistic effect renders the inventive medicaments suitable for treating metabolic disorders and/or eating disorders, in particular, obesity, bulimia, anorexia, hyperphagia and diabetes.
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Page/Page column 221-222
(2008/06/13)
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- Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds
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The present invention relates to alkyne compounds of general formula I wherein the groups and residues A, B, W, X, Y, Z, R1 and R2 have the meanings given in claim 1. The invention further relates to pharmaceutical compositions containing at least one alkyne according to the invention. In view of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.
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- Synthesis and 2nd order nonlinear optical properties of soluble polyimides bearing nitroazobenzene type chromophore pendants attached in side-on mode
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An organic soluble polyimide was prepared from 3,3′-dihydroxybenzidine and 2,2-bis(phthalic anhydride)hexafluoropropane. The two hydroxy groups in the repeating unit of the polyimide thus prepared were utilized in attaching 4-nitro-4′-diphenylaminoazobenz
- Jeon, Bong-Jin,Soon, Wook Cha,Jeong, Mi-Yun,Tong, Kun Lim,Jin, Jung-Il
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p. 546 - 552
(2007/10/03)
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- 4,4-(disubstituted) cyclohexan-1-one monomers and related compounds
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This invention relates to derivatives of 4,4-(disubstituted)cyclohexan-1-ones and related compounds which are useful for treating allergic and inflammatory diseases.
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- Synthetic use of poly[4-(diacetoxyiodo)styrene] for organic reactions
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Poly[4-(diacetoxyiodo)styrene] is sufficiently reactive for the iodination of aromatics, the oxidative 1,2-aryl migration of alkyl aryl ketones, the α-hydroxylation of ketones, and the oxidation of hydroquinones and sulfides similarly to (diacetoxyiodo)benzene. Here, those reactions with poly[4-(diacetoxyiodo)styrene] are very useful because of the simple operation; thus, filtration gives the crude products and recovered poly(4- iodostyrene), and then poly[4-(diacetoxyiodo)-styrene] can be regenerated by oxidation of the recovered poly(4-iodostyrene), which are reused for the same reactions.
- Togo, Hideo,Abe, Seiichiro,Nogami, Genki,Yokohama, Masataka
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p. 2351 - 2356
(2007/10/03)
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- Synthetic application of poly[styrene(iodoso diacetate)]
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Poly[styrene(iodoso diacetate)] is sufficiently reactive to effect the iodination of aromatics and oxidative 1,2-aryl migration of alkyl aryl ketones as (diacetoxyiodo)benzene, and can be regenerated and reused for the same reactions.
- Togo, Hideo,Nogami, Genki,Yokoyama, Masataka
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p. 534 - 536
(2007/10/03)
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- Formation and synthetic use of oxygen-centred radicals with (diacetoxyiodo)arenes
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o-Alkyl- or o-aryl-benzenecarboxylic acids and alcohols containing an aromatic ring are treated with a (diacetoxyiodo)arene-iodine system to give the corresponding cyclized products such as phthalide, benzocoumarin and chromane derivatives in moderate to good yields via the corresponding oxygen-centred radicals. For the carboxylic acids, [bis(trifluoroacetoxy)iodo]benzene functions effectively, while (diacetoxyiodo)benzene is effective for the alcohols. Chromane and its derivatives are obtained as iodinated compounds by hypoiodite species derived from (diacetoxyiodo)benzene and iodine. Copyright 1997 by the Royal Society of Chemistry.
- Togo, Hideo,Muraki, Takahito,Hoshina, Yoichiro,Yamaguchi, Kentaro,Yokoyama, Masataka
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p. 787 - 793
(2007/10/03)
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- Remote functionalization: Cyclic alkoxylation onto aromatic ring via radical pathway
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Oxidative cyclization of alcohols containing an aromatic ring with (diacetoxyiodo)benzene and iodine gave the corresponding cyclic ethers via alkoxy radicals in good yields. The present method is very useful for the direct preparation of flavonoid and vitamin E analogues from the alcohols.
- Muraki,Togo,Yokoyama
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p. 2441 - 2444
(2007/10/03)
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- Phenethanolamine compounds
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The invention provides compounds of the general formula (I) STR1 wherein the substituents are defined in the specification, and physiologically acceptable salts and solvates thereof. The compounds of formula (I) have a selective stimulant action at β2 -adrenoreceptors and are useful, in particular in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.
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