- Probing cytochrome P450 (CYP) bioactivation with chloromethylindoline bioprecursors derived from the duocarmycin family of compounds
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The duocarmycins belong to a class of agent which has great potential for use in cancer therapy. Their exquisite potency means they are too toxic for systemic use, and targeted approaches are required to unlock their clinical potential. In this study, we
- Ortuzar, Natalia,Karu, Kersti,Presa, Daniela,Morais, Goreti R.,Sheldrake, Helen M.,Shnyder, Steve D.,Barnieh, Francis M.,Loadman, Paul M.,Patterson, Laurence H.,Pors, Klaus,Searcey, Mark
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supporting information
(2021/05/04)
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- NOVEL MEDICINE COMPOSED OF BENZIMIDAZOLE COMPOUND
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PROBLEM TO BE SOLVED: To provide an agent for treating or preventing a disease associated with SCN9A(Nav1.7). SOLUTION: The present invention provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. [R1a, R1b, R1c, R1d: H, halogen, cyano, C1-4 alkyl, C1-4 alkoxy or the like. R2, R3: H, C1-6 alkyl, C3-10 cycloalkyl or the like. R4: H, C1-6 alkyl, C3-7 cycloalkyl or the like. m: 1, 2 or 3. L: CR7R8(R7, R8: H, OH, C1-4 alkyl, C1-4 alkoxy or the like)]. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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Paragraph 0179; 0180
(2018/11/02)
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- COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING CFTR
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The present disclosure is directed to disclosed compounds that modulate, e.g., address underlying defects in cellular processing of CFTR activity.
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Paragraph 0237; 0243
(2017/08/01)
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- NOVEL BENZIMIDAZOLE COMPOUND AND MEDICAL USE THEREOF
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The present invention provides a medicament for treating a disease involving Nav 1.7 such as neuropathic pain, nociceptive pain, inflammatory pain, small-fiber neuropathy, erythromelalgia, paroxysmal extreme pain disorder, dysuria, and multiple sclerosis, which comprises a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R1c and R1d are hydrogen, halogen, cyano, C1-4 alkyl, C1-4 alkoxy, or the like, provided that at least one of R1a, R1b, R1c and R1d is C6-10 aryl, C6-10 aryloxy, or the like, R2 and R3 are hydrogen, C1-6 alkyl, C3-10 cycloalkyl, or the like, R4 is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, or the like, m is 1, 2 or 3, L is CR7R8, and R7 and R8 are hydrogen, hydroxyl, C1-4 alkyl, C1-4 alkoxy, or the like.
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Paragraph 0507; 0508
(2017/08/01)
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- ORGANIC COMPOUNDS
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The present invention relates to novel PDE2 inhibitory compounds of Formula I as described above, their use as pharmaceuticals and pharmaceutical compositions comprising them.
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Paragraph 0036
(2016/06/28)
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- NOVEL IMAGING AGENTS FOR DETECTING NEUROLOGICAL DYSFUNCTION
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Disclosed here in are compounds and methods of diagnosing Alzheimer's Disease or a predisposition thereto in a mammal, the method comprising administering to the mammal a diagnostically effective amount of a radiolabeled compound, wherein the compound is selected from the group consisting of radiolabeled flavones, coumarins, carbazoles, quinolinones, chromenones, imidazoles and triazoles derivatives, allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing Alzheimer's Disease
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Page/Page column 98
(2009/10/09)
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- Improved synthesis of functionalized mesogenic 2,6-bisbenzimidazolylpyridine ligands
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A versatile one-pot synthetic platform for the preparation of a range of functionalized 2,6-bisbenzimidazolylpyridine (Bip) derivatives is presented. This protocol significantly reduces the cost and time of previous synthetic routes, while facilitating sc
- McKenzie, Blayne M.,Miller, Adriane K.,Wojtecki, Rudy J.,Johnson, J. Casey,Burke, Kelly A.,Tzeng, Karis A.,Mather, Patrick T.,Rowan, Stuart J.
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p. 8488 - 8495
(2008/12/20)
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- FUSED HETEROCYCLIC DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME,AND MEDICINAL USE THEREOF
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The present invention provides a compound useful as an agent for the prevention or treatment of a sex hormone-dependent disease or the like. That is, the present invention provides a fused heterocyclic derivative represented by the following general formula (I), a pharmaceutical composition containing the same, a medicinal use thereof and the like. In the formula (I), ring A represents 5-membered cyclic unsaturated hydrocarbon or 5-membered heteroaryl; RA represents halogen, alkyl, alkenyl, alkynyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl or the like; ring B represents aryl or heteroaryl; RB represents halogen, alkyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl or the like; E1 and E2 represent an oxygen atom or the like; U represents a single bond or alkylene; X represents a group represented by Y, -SO2-Y, -O-(alkylene)-Y, -O-Z in which Y represents Z, amino or the like; Z represents cycloalkyl, heterocycloalkyl, aryl, heteroaryl or the like; or the like.
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Page/Page column 16
(2008/12/06)
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- Indole derivatives with vascular damaging activity
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The invention provides a compound of Formula (I) wherein: R1 and R2 are independently selected from hydrogen, halogen, —CN, a hydrocarbyl group or a group of Formula (II); wherein W is aryl or a heterocyclic group, R4 is independently select from hydrogen, halogen, —OH, amino, alkanoylamino, —OPO3H2, or a hydrocarbyl group, wherein the amino group is optionally substituted by an amino acid residue and the hydroxy group is optionally esterified or two R4 groups together form an optionally substituted cyclic or heterocyclic group; X is selected from Μ(y) S+—, +—O—+, —+S(O)+—, —+S(O2)+— and —+NH—; p is an integer from 0 to 4; and q is an integer from 1 to 4; R3 and R10 are independently selected from hydrogen, lower alkyl or a group of Formula (IV): wherein Y is selected from +NH+—, —Μ(Y)OΜ(Y)— or a bond; Z is selected from +NH+—, —+Oν—, —+C(O)+— or a bond; r is an integer from 0 to 4; t is an integer from 0 to 1; R6 is hydrogen, a hydrocarbyl group or a group of Formula (V): wherein n is an integer of from 1 to 6, and; R7 and R8 are independently selected from hydrogen or a hydrocarbyl group; and R11 is hydrogen or lower alkyl; or a salt or solvate thereof; provided that: I) when R1 is an unsubstituted phenylthio group (Ph—S—), R2 is H, R10 is H and R11 is H then R3 is neither H nor —C(O)—O—CH2CH3; and ii) R1, R2 and R3 are not all hydrogen. Such compounds are predicted to cause the selective destruction of tumour vasculature. They may therefore be used to inhibit and/or reverse, and/or alleviate symptoms of angiogenesis and/or any disease state associated with angiogenesis.
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- Substituted 4-phthalimidocarboxanilides as inhibitors of purine salvage phosphoribosyltransferases
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The use of certain heterocyclic derivatives for treating parasitic protozoa infections in mammals, in particular bovine trichomoniasis and giardiasis, is disclosed.
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- AN ALTERNATIVE METHOD FOR SYNTHESIS OF THE CC-1065 PHARMACOPHORE, 1,2,7,7a-TETRAHYDROCYCLOPROPINDOL-4-ONE
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The synthesis of the CC-1065 pharmacophore, 2-(1-methylpyrrole-2-carbonyl)-1,2,7,7a-tetrahydrocyclopropindol-4-one (17), is described.The methods reported here provide an alternative route for the synthesis of compounds possessing the biologically
- Wang, Yugiang,Lown, J. William
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p. 1399 - 1410
(2007/10/02)
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- 4H-1-benzopyran-4-one derivative or its salt, process for producing the same and pharmaceutical composition comprising the same as active ingredient
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This invention relates to a 4H-1-benzopyran-4-one derivative represented by the formula: STR1 or a salt thereof, a process for producing the same and a pharmaceutical composition comprising the same as active ingredient.
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- Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065
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The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effectiv
- Warpehoski,Gebhard,Kelly,Krueger,Li,McGovren,Prairie,Wicnienski,Wierenga
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p. 590 - 603
(2007/10/02)
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