- SUBSTITUTED N-ARYL BENZAMIDES AND RELATED COMPOUNDS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES
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Substituted diaryl compounds of the Formulae (I, II, III), where the variables are as defined in the claims, and their pharmaceutically acceptable derivatives, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including A? amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided.
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Page/Page column 71; 81
(2008/06/13)
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- BENZENE DERIVATIVES,PROCESS FOR PREPARING THE SAME AND USE THEREOF
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Novel benzene derivatives represented by the formula (I) : wherein R1, R4 and R6 each independently represents a hydrogen atom, a halogen atom or a hydrocarbon group, R2 represents a hydrocarbon group or a heterocyclic group, R3 represents a hydrocarbon group, NR7'R7 or OR8 (wherein R7' represents a hydrogen atom or a hydrocarbon group, R7 represents a non-aromatic group, or R7' and R7 may form a ring with the adjacent nitrogen atom, and R8 represents a hydrocarbon group or a heterocyclic group), R5 represents a hydrocarbon group or a heterocyclic group (except for a quinolyl group), R5' represents a hydrogen atom, or a hydrocarbon group, or R5 and R5' may form a ring with the adjacent nitrogen atom, and R5" represents a hydrogen atom or a hydrocarbon group, which have vanilloid receptor agonist activity and are useful as a drug such as an analgesic and an agent for preventing and/or treating urinary frequency and/or urinary incontinence.
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- Synthesis of pyrrolo[4,3,2-de]quinolines from 6,7-dimethoxy-4-methylquinoline. Formal total syntheses of damirones A and B, batzelline C, isobatzelline C, discorhabdin C, and makaluvamines A-D
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2-Amino-4-nitrophenol and 2-methoxy-5-nitroaniline were converted into the 5-nitroquinolines 6b and 6d, respectively, and then the latter into nitro-acetal 6f. 6,7-Dimethoxy-4-methylquinoline (6g) was nitrated at C-5 and then the methyl substituent conver
- Roberts, David,Joule, John A.,Antonieta Bros,Alvarez, Mercedes
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p. 568 - 577
(2007/10/03)
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- Potential Antitumor Agents. 36. Quanitative Relationships between Experimental Antitumor Activity, Toxicity, and Structure for the General Class of 9-Anilinoacridine Antitumor Agents
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Quantitative relationships (QSAR) have been derived between antileukemic (L1210) activity and agent physicochemical properties for 509 tumor-active members of the general class of 9-anilinoacridines.One member of this class is the clinical agent m-AMSA (NSC 249992).Agent hydrophobicity proved a significant but not a dominant influence on in vivo potency.The electronic properties of substituent groups proved important, but the most significant effects on drug potency were shown by the steric influence of groups placed at various positions on the 9-anilinoacridine skeleton.The results are entirely consistent with the physiologically important step in the action of these compounds being their binding to double-stranded DNA by intercalation of the acridine chromophore between the base pairs and positioning of the anilino group in the minor groove, as previously suggested.An equation was also derived for the acute toxicities of 643 derivatives of 9-anilinoacridine.This equation took a somewhat similar form to the one modeling antileukemia potency, emphasizing the usual fairly close relationship between potency and acute toxicity for antitumor agents in general.This study demonstrated the power of QSAR techniques to structure very large amounts of biological data and to allow the extraction of useful information from bearing on the possible site of action of the compounds concerned.
- Denny, William A.,Cain, Bruce F.,Atwell, Graham J.,Hansch, Corwin,Panthananickal, Augustine,Leo, A.
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p. 276 - 300
(2007/10/02)
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