- Catalytic Enantioselective Synthesis of Axially Chiral Diarylmethylidene Indanones
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We describe the first atropselective Suzuki-Miyaura cross-coupling of β-keto enol triflates to access axially chiral (Z)-diarylmethylidene indanones (DAIs). The chemical, physical, and biological properties of DAIs are unknown, despite their being structurally similar to arylidene indanones, primarily due to the lack of racemic or chiral methods. Through this work, we demonstrate a general and efficient protocol for the racemic as well as the atropselective synthesis of (Z)-DAIs. An unusual intramolecular Morita-Baylis-Hillman reaction is utilized for the Z-selective synthesis of β-keto enol triflates.
- Kumar, Prashant,Shirke, Rajendra P.,Yadav, Sonu,Ramasastry
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supporting information
p. 4909 - 4914
(2021/06/30)
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- Analogues of fenarimol are potent inhibitors of trypanosoma cruzi and are efficacious in a murine model of chagas disease
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We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor of Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, and the results of structure-activity investigations leading to potent analogues with low nM IC50s in a T. cruzi whole cell in vitro assay. Lead compounds suppressed blood parasitemia to virtually undetectable levels after once daily oral dosing in mouse models of T. cruzi infection. Compounds are chemically tractable, allowing rapid optimization of target biological activity and drug characteristics. Chemical and biological studies undertaken in the development of the fenarimol series toward the goal of delivering a new drug candidate for Chagas disease are reported.
- Keenan, Martine,Abbott, Michael J.,Alexander, Paul W.,Armstrong, Tanya,Best, Wayne M.,Berven, Bradley,Botero, Adriana,Chaplin, Jason H.,Charman, Susan A.,Chatelain, Eric,Von Geldern, Thomas W.,Kerfoot, Maria,Khong, Andrea,Nguyen, Tien,McManus, Joshua D.,Morizzi, Julia,Ryan, Eileen,Scandale, Ivan,Thompson, R. Andrew,Wang, Sen Z.,White, Karen L.
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supporting information; experimental part
p. 4189 - 4204
(2012/07/27)
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- PYRROLOPYRIMIDINE ALKYNYL COMPOUNDS AND METHODS OF MAKING AND USING SAME
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Provided herein are pyrrolopyrimide alkynyl compounds, and methods of making and using the same. Such compounds may be used in inflammatory or myeloproliferative disorders. The disclosure also provides for treating cancer.
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Page/Page column 59
(2009/05/30)
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- (Phenylpiperidinyl)cyclohexylsulfonamides: Development of α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS)
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Although α1 adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by CV-related side-effects that are caused by the subtype non-selec
- Chiu, George,Li, Shengjian,Connolly, Peter J.,Pulito, Virginia,Liu, Jingchun,Middleton, Steven A.
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p. 3930 - 3934
(2008/02/11)
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- Phenylsulfonyl-1,3-dihydro-2h-indole-2-one derivatives, their preparation and their therapeutic use
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The invention relates to compounds of formula: and also to the salts thereof with mineral or organic acids, and the solvates and/or hydrates thereof, with affinity for and selectivity towards the arginine-vasopressin V1b receptors and/or for the ocytocin receptors and, furthermore, for certain compounds, affinity for the V1a receptors. The invention also relates to the process for preparing them, to the intermediate compounds of formula (IV) that are useful for preparing them, to pharmaceutical compositions containing them and to their use for preparing medicinal products.
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Page/Page column 18-19
(2010/02/08)
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- Serotonin 5-HT1A and dopamin D2 receptor ligands
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The present invention relates to a novel series of 4-phenylpiperazines, 4-phenylpiperidines and 4-phenyl-1,2,3,6-tetrahydropyridines compounds of general formula (I) wherein A is alkylene, alkenylene, alkynylene, and C3-7cycloalkylene; R1is a C3-10alkyl, alkenyl, or alkynyl group, cycloalk(en)yl, cycloalk(en)yl-alk(en/yn)yl, trifluoromethylsulfonyl, or alkylsulfonyl, R2-R5are optional substituents; R9and R10are hydrogen, alkyl or together form an ethylene or propylene bridge; W is O or S; V is O, S, CR6R7, or NR8wherein R6, R7, and R8are hydrogen or alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, optionally substituted arylalkyl or aryl, or R6and R7constitute a 3-7 membered spiro ring; Z is —(CH2)m—, m being 2 or 3 or Z is —CH═CH—; X is N, C or CH; show effects on central serotonin 5-HT1Aand dopamine D2receptors. Thus the novel compounds are useful in the treatment of certain psychic and neurologic disorders, in particular psychosis.
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- ALKYLOXYAMINO SUBSTITUTED FLUORENONES AND THEIR USE AS PROTEIN KINASE C INHIBITORS
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The present invention describes certain alkyloxyamino-substituted fluorenones which inhibit protein kinase C, as well as pharmaceutical compositions including these compounds and methods of using these compounds to control protein kinase C activity in mammals, including humans. More specifically, the present compounds are useful for the treatment of neoplastic disease states, disorders associated with abnormal blood flow (including hypertension, ischemia, atherosclerosis, coagulation disorders), and inflammatory diseases (including immune disorders, asthma, lung fibrosis, and psoriasis).
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- Anomalous substituent effects in the Bischler-Napieralski reaction of 2-aryl aromatic formamides
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Treatment of some 1-naphthylformamides (or formanilides) possessing a 2,4,5-trioxygenated phenyl substituent at the 2-position with POCl3 caused an unprecedented carbon insertion reaction into a benzene ring, producing 7-5 ring (azaazulene) systems as valence isomers of isoquinoline skeletons. Precise examination of this abnormal Bischler-Napieralski reaction (BNR) using various substrates led to the following scope and limitations: (i) the 7-5 ring systems were constructed when either 2-alkoxy-4,5-methylenedioxyphenyl- or 4,5-dialkoxy-2-hydroxyphenyl-substituted formamides were used as a starting substrate; (ii) in the former case the formyl carbon was inserted into the C1-C6 bond of the 2-phenyl group, and normal isoquinoline cyclization competed with an abnormal carbon insertion reaction; (iii) the presence of a hydroxy group at the 2′-position as in the latter cases caused exclusive carbon insertion, in which alternative C1-C2 insertion products were quantitatively formed; (iv) 3,6-dimethoxy-2-hydroxyphenyl-substituted formanilide electronically equivalent to 4,5-dialkoxy-2-hydroxy derivatives produced an indole-pyrone as an abnormal BNR product. Theoretical approaches using the PM-3 method indicated that these abnormal BNRs could be triggered by ipso attack at the 1′-position yielding spiro intermediates. Ring cleavege of the six-membered ring in the spiro intermediates to a ketene function followed by recyclization was proposed for the 2′-hydroxy-directed abnormal BNRs leading to the C1-C2 insertion product or the indole-pyrone derivative.
- Ishikawa,Shimooka,Narioka,Noguchi,Saito,Ishikawa,Yamazaki,Harayama,Seki,Yamaguchi
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p. 9143 - 9151
(2007/10/03)
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- Orally active benzamide antipsychotic agents with affinity for dopamine D2, serotonin 5-HT(1A), and adrenergic α1 receptors
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New antipsychotic drugs are needed because current therapy is ineffective for many schizophrenics and because treatment is often accompanied by extrapyramidal symptoms and dyskinesias. This paper describes the design, synthesis, and evaluation of a series of related (aminomethyl)benzamides in assays predictive of antipsychotic activity in humans. These compounds had notable affinity for dopamine D2, serotonin 5- HT(1A), and α1-adrenergic receptors. The arylpiperazine 1-[3-[[4-[2-(1- methylethoxy)phenyl]-1-piperazinyl]methyl]benzoyl]piperidine (mazapertine, 6) was chosen because of its overall profile for evaluation in human clinical trials. The corresponding 4-arylpiperidine derivative 67 was also highly active indicating that the aniline nitrogen of 6 is not required for activity. Other particularly active structures include homopiperidine amide 14 and N-methylcyclohexylamide 31.
- Reitz, Allen B.,Baxter, Ellen W.,Codd, Ellen E.,Davis, Coralie B.,Jordan, Alfonzo D.,Maryanoff, Bruce E.,Maryanoff, Cynthia A.,McDonnell, Mark E.,Powell, Eugene T.,Renzi, Michael J.,Schott, Mary R.,Scott, Malcolm K.,Shank, Richard P.,Vaught, Jeffry L.
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p. 1997 - 2009
(2007/10/03)
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- 4-ARYLPIPERAZINES AND 4-ARYLPIPERIDINES
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Compounds of the general formula I: STR1 are disclosed as novel antipsychotic agents.
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