- TAU-PROTEIN TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of tan protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tan protein, such that tan protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tan. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tan protein. Diseases or disorders that result from aggregation or accumulation of tan protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1557; 1558
(2021/02/12)
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- AMINOISOXAZOLINE COMPOUNDS AS AGONISTS OF ALPHA7-NICOTINIC ACETYLCHOLINE RECEPTORS
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The present invention relates to novel aminoisoxazoline compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.
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Paragraph 00294; 00295
(2017/05/19)
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- PYRROLO[2,3-C]PYRIDINES AS IMAGING AGENTS FOR NEUROFIBRILARY TANGLES
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Pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts are disclosed, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha- synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, the compounds are used as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. Futher, the compounds are useful for measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.
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Page/Page column 56
(2016/01/01)
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- TRPV1 ANTAGONISTS
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Disclosed herein are compounds of Formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 88-89
(2010/04/30)
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- TRPV1 ANTAGONISTS
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Disclosed herein are compounds of formula (I), or pharmaceutically acceptable salts, solvates, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 87
(2010/04/30)
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- SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
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The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).
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Page/Page column 136; 137
(2010/11/18)
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- In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists
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The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino) benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.
- Perner, Richard J.,DiDomenico, Stanley,Koenig, John R.,Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Drizin, Irene,Guo, Zhu Zheng,Turner, Sean C.,Jinkerson, Tammie,Brown, Brian S.,Keddy, Ryan G.,Lukin, Kurill,McDonald, Heath A.,Honore, Prisca,Mikusa, Joe,Marsh, Kennan C.,Wetter, Jill M.,St. George, Karen,Jarvis, Michael F.,Faltynek, Connie R.,Lee, Chih-Hung
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p. 3651 - 3660
(2008/02/12)
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- Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
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Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity, wherein X1, X2, X3, X4, X5, R5, R6, R7, R8a, R8b, R9, Z1, Z2 and L are as defined in the description.
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- Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
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Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.
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Page/Page column 30
(2010/02/11)
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- Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
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Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.
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- Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
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Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.
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- 3-Chloro-5-acetamidaisoquinoline as a herbicide
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Biologically active compositions of matter comprising substituted isoquinolines and salts thereof. Certain of the compounds and their salts are novel. Acaricidal, fungicidal, herbicidal and insecticidal activity is demonstrated. In particular 3-chloro-5-acetamido-isoquinoline shows good activity as a selective pre-emergence herbicide, and 4-bromo-5-nitro-isoquinoline shows good fungicidal activity against Erysiphe graminis (wheat powdery mildew).
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