- C-5 substituted heteroaryl-3-pyridinecarbonitriles as PKCθ inhibitors: Part II
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We previously reported that a 3-pyridinecarbonitrile analog with a furan substituent at C-5 and a 4-methylindol-5-ylamino substituent at C-4, 1, was a potent inhibitor of PKCθ (IC50 = 4.5 nM). Replacement of the C-5 furan ring of 1 with bicycli
- Prashad, Amar S.,Wang, Daniel,Subrath, Joan,Wu, Biqi,Lin, Melissa,Zhang, Mei-Yi,Kagan, Natasha,Lee, Julie,Yang, Xiaoke,Brennan, Agnes,Chaudhary, Divya,Xu, Xin,Leung, Louis,Wang, Jack,Boschelli, Diane H.
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Read Online
- P2X3 AND/OR P2X2/3 COMPOUNDS AND METHODS
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The present disclosure provides novel compounds and methods for preparing and using these compounds. In one embodiment, the compounds are of the structure of formula (I), wherein R1-R7 are defined herein. In a further embodiment, these compounds are useful in method for regulating one or both of the P2X3 or P2X2/3 receptors. In another embodiment, these compounds are useful for treating pain in patients by administering one or more of the compounds to a patient. In another embodiment, these compounds are useful for treating respiratory dysfunction in patients by administering one or more of the compounds to a patient.
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Paragraph 0174-0177
(2018/04/17)
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- Heterocyclic acene propanoic derivative as well as preparation method and application thereof
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The invention relates to a heterocyclic acene propanoic derivative as well as a preparation method and application thereof. A structural formula of the derivative is shown in the description. The heterocyclic acene propanoic derivative shows agonist activ
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Paragraph 0188; 0190; 0191; 0192
(2018/01/09)
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- Substituted Pyran Derivatives
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Certain 3,6-disubstituted and 2, 4, 5-trisubstituted pyran derivatives that exhibit potent activity on monoamine transport systems are provided. The 3, 6 and 2, 4, 5 pyrans are useful in probing the effects of their binding to monoamine transporter system
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Paragraph 0074; 0075; 0076; 0077
(2014/10/29)
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- Substituent effects of cis-cinnamic acid analogues as plant growh inhibitors
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1-O-cis-Cinnamoyl-β-d-glucopyranose is one of the most potent allelochemicals that has been isolated from Spiraea thunbergii Sieb by Hiradate et al. It derives its strong inhibitory activity from cis-cinnamic acid (cis-CA), which is crucial for phytotoxicity. By preparing and assaying a series of cis-CA analogues, it was previously found that the key features of cis-CA for lettuce root growth inhibition are a phenyl ring, cis-configuration of the alkene moiety, and carboxylic acid. On the basis of a structure-activity relationship study, the substituent effects on the aromatic ring of cis-CA were examined by systematic synthesis and the lettuce root growth inhibition assay of a series of cis-CA analogues having substituents on the aromatic ring. While ortho- and para-substituted analogues exhibited low potency in most cases, meta-substitution was not critical for potency, and analogues having a hydrophobic and sterically small substituent were more likely to be potent. Finally, several cis-CA analogues were found to be more potent root growth inhibitors than cis-CA.
- Nishikawa, Keisuke,Fukuda, Hiroshi,Abe, Masato,Nakanishi, Kazunari,Taniguchi, Tomoya,Nomura, Takashi,Yamaguchi, Chihiro,Hiradate, Syuntaro,Fujii, Yoshiharu,Okuda, Katsuhiro,Shindo, Mitsuru
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p. 132 - 147
(2014/01/06)
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- 2-{3-[4-(Alkylsulfinyl)phenyl]-1-benzofuran-5-yl}-5-methyl-1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3β with good brain permeability
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Glycogen synthase kinase 3β (GSK-3β) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3β inhibitors, however,
- Saitoh, Morihisa,Kunitomo, Jun,Kimura, Eiji,Iwashita, Hiroki,Uno, Yumiko,Onishi, Tomohiro,Uchiyama, Noriko,Kawamoto, Tomohiro,Tanaka, Toshimasa,Mol, Clifford D.,Dougan, Douglas R.,Textor, Garret P.,Snell, Gyorgy P.,Takizawa, Masayuki,Itoh, Fumio,Kori, Masakuni
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experimental part
p. 6270 - 6286
(2010/03/24)
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- INDOLE-SUBSTITUTED 3-CYANOPYRIDINES AS KINASE INHIBITORS
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Disclosed are compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X is -O-, -N(R3)-, -S-, -S(O)- or -S(O)2-; R2 is a C1-4 alkyl group or -CF3; and R1, R3, R4 and p are as defined herein; wherein the compounds are useful as kinase inhibitors. Also disclosed are pharmaceutical compositions containing, and intermediate compounds and methods for making the compounds of formula (I) and their pharmaceutically acceptable salts; and methods of using the foregoing to treat inflammatory and autoimmune diseases such as asthma, colitis, multiple sclerosis, psoriasis, arthritis, rheumatoid arthritis, inflammatory bowel disease, and joint inflammation.
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Page/Page column 41
(2009/07/17)
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- Substituted Cyanopyridines as protein kinase inhibitors
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The present teachings provide compounds of formula I and their pharmaceutically acceptable salts, hydrates, and esters, wherein R1, R2, and X are as defined herein. The present teachings also provide methods of making the compounds of formula I, and methods of treating autoimmune and inflammatory diseases by administering a therapeutically effective amount of a compound or compounds of formula I to a mammal including a human.
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Page/Page column 25
(2008/06/13)
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- An isomerization-ring-closing metathesis strategy for the synthesis of substituted benzofurans
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Twelve substituted benzofurans were synthesized from their corresponding substituted 1-allyl-2-allyloxybenzenes using ruthenium-mediated C- and O-allyl isomerization followed by ring-closing metathesis.
- Van Otterlo, Willem A.L.,Morgans, Garreth L.,Madeley, Lee G.,Kuzvidza, Samuel,Moleele, Simon S.,Thornton, Natalie,De Koning, Charles B.
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p. 7746 - 7755
(2007/10/03)
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- ISOTHIAZOLE DIOXIDES AS CXC- AND CC- CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (IA): and the pharmaceutically acceptable salts and solvates thereof. D and E are different groups wherein one is N and the other is CR50. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of formula IA.
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Page/Page column 318
(2010/02/13)
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- THIADIAZOLES AS CXC- AND CC- CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of Formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and ischemia reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of Formula (IA).
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Page/Page column 209
(2010/02/12)
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- THIADIAZOLEDIOXIDES AND THIADIAZOLEOXIDES AS CXC- AND CC-CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, acute pain, acute and chronic inflammatory pain, and neuropathic pain using a compound of formula (IA).
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Page 239-240; 348
(2008/06/13)
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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- 3,4-DI-SUBSTITUTED CYCLOBUTENE-1, 2-DIONES AS CXC-CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof. Also disclosed is the treatment of chemokine-mediated diseases using compounds of the formula (II)
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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- AZOLIDINONE-VINYL FUSED-BENZENE DERIVATIVES
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The present invention is related to azolidinedione-vinyl fused-benzene derivatives of formula (I) for the treatment and/or prophylaxis of autoimmune disorders and/or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, graft rejection or lung injuries. Formula (I), wherein A, X, Y, Z, R1 , R2 and n are as described in the description.
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- Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists
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The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N- dibutylacetamido)-4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3- carboxylic acid (A-127722). This is a potent antagonist, binding to the ET(A) and ET(B) receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole. While this compound was seemingly optimized at its N-terminus, no effort had been directed toward understanding the contributions to binding affinity or receptor subtype selectivity conferred by the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists. Oxygenated benzenes, such as p- anisyl, were potent compounds with IC50s in the low-nanomolar range. Simple deletion of either of the two oxygen atoms (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar affinity for the ET(A) receptor. Additionally, the compounds showed enhanced selectivity, binding to the ET(B) receptor subtype in the micromolar range. This paper describes the development of this novel class of compounds.
- Tasker, Andrew S.,Sorensen, Bryan K.,Jae, Hwan-Soo,Winn, Martin,Von Geldern, Thomas W.,Dixon, Douglas B.,Chiou, William J.,Dayton, Brian D.,Calzadila, Samuel,Hernandez, Lisa,Marsh, Kennan C.,WuWong, J. Ruth,Opgenorth, Terry J.
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p. 322 - 330
(2007/10/03)
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- An Alternative Route to a Benzofuran Natural Product Dehydrotremetone
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Dehydrotremetone, a toxic ketone isolated from the weeds Eupatorium urticaefolium and Aplopappus heterophyllus, has been synthesized from isovanillin via palladium-mediated cross-coupling reaction and lithium chloride-mediated concurrent demethylation-ben
- Hiroya, Kou,Hashimura, Kazuya,Ogasawara, Kunio
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p. 2463 - 2472
(2007/10/02)
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- 5-[Substituted bicyclic aryl or heteroaryl]cyclohexane-1,3-dione herbicides
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The invention concerns novel compounds of the formula I STR1 wherein: A is selected from CH and N; B is selected from oxygen, sulfur, CH2 and the group N-Z wherein Z is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cy
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