- SELF-IMMOLATIVE LINKERS CONTAINING MANDELIC ACID DERIVATIVES, DRUG-LIGAND CONJUGATES FOR TARGETED THERAPIES AND USES THEREOF
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The invention provides a therapeutic drug and targeting conjugate, pharmaceutical compositions containing these conjugates in pharmaceutical composition, and uses of these conjugates in anti-neoplastic and other therapeutic regimens. Also provided are novel intermediates thereof. The conjugates provide a therapeutic drug fragment or prodrug fragment bound to a targeting moiety via a linker which comprises a substrate cleavable by a protease such as Cathepsin B. The targeting moiety is a ligand which targets a cell surface molecule, such as a cell surface receptor on an anti-neoplastic cell. The ligand may function solely as a targeting moiety or may itself have a therapeutic effect. Following administration of the therapeutic drug and targeting conjugate of formula I and exposure of the conjugate to the protease specific for the substrate, the linker is cleaved and the targeting moiety is separated from the conjugate, which causes the drug fragment or prodrug fragment to convert to the drug or prodrug. The recited conjugates are useful in anti-neoplastic therapies. Also provided are methods of making the therapeutic drug and targeting conjugates and intermediates thereof, and kits comprising the therapeutic drug and targeting conjugates.
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Page/Page column 72; 134; 135
(2015/03/28)
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- NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES
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The invention provides compounds of general formula (I) wherein A, B, p, w, x, y, and z are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
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Page/Page column 86; 87
(2008/06/13)
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- Cyclohexyl derivatives and their use as therapeutic agents
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The present invention relates compounds of the formula (I): wherein ring A is a phenyl or pyridyl ring; X represents a linker selected from the group consisting of: (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l) and R1, R2, R3, R4, R5, R6, R7, R13, R14, R15, R16, R?17, R18, R19, R21a and R21b are as defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia.
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- Cyclohexane derivatives and their use as therapeutic agents
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The present invention relates compounds of formula (I), wherein ring A is a phenyl or pyridyl ring; X represents a linker selected from the group consisting of formulae: (a), (b), (c), (d), and (e); and R1, R2, R3, R4, R5, R6, R7, R13, R14, R15, R16, R17, R21a and R21b are as defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia.
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- 4,4-Disubstituted cyclohexylamine NK1 receptor antagonists II
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A series of novel 4,4-disubstituted cyclohexylamines as NK1 receptor antagonists is described: modifications to the amine moiety retain NK1 receptor binding affinity whilst disrupting IKr affinity.
- Cooper, Laura C.,Carlson, Emma J.,Castro, Jose L.,Chicchi, Gary G.,Dinnell, Kevin,Di Salvo, Jerry,Elliott, Jason M.,Hollingworth, Gregory J.,Kurtz, Marc M.,Ridgill, Mark P.,Rycroft, Wayne,Tsao, Kwei-Lan,Swain, Christopher J.
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p. 1759 - 1762
(2007/10/03)
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- N-acyl cyclic amine derivatives
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The invention relates to compounds represented by the general formula [I][wherein Ar means an aryl group or a heteroaryl group which may have a substitutive group selected from a group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group; R1 means a C3-C6 cycloalkyl group which is substitutable with a fluorine atom; R2 and R4 mean hydrogen atoms, groups represented by -(A1)m-NH-B or the like; R3 and R5 mean hydrogen atoms, C1-C6 aliphatic hydrocarbon groups or the like which are substitutable with a lower alkyl group(s); n means 0 or 1; and X means an oxygen atom or a sulfur atom]. Compounds according to the invention, since they not only have potent selective antagonistic activity against muscarinic M3 receptors but also exhibit excellent oral activity, durability of action and pharmacokinetics, are very useful as safe and effective remedies against respiratory, urinary and digestive diseases with little adverse side effects.
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