- PLANT GROWTH REGULATOR COMPOUNDS
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The present invention relates to relates to novel strigolactone derivatives of formula (I), to processes for preparing these derivatives including intermediate compounds, to seeds comprising these derivatives, to plant growth regulator or seed germination promoting compositions comprising these derivatives and to methods of using these derivatives in controlling the growth of plants and/or promoting the germination of seeds.
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Page/Page column 29; 31
(2018/04/13)
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- Asymmetric Organocatalytic Synthesis of Bisindoles – Scope and Derivatizations
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Starting from 3-vinylindoles and glyoxolate imines, we created a library of diverse 4,6-bis(1H-indole-3-yl)piperidine 2-carboxylates by using 10 mol-% of a chiral phosphoric acid. Utilising electron-withdrawing groups on the starting material during the r
- Retich, Christina,Br?se, Stefan
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supporting information
p. 60 - 77
(2018/01/17)
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- Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7
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A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the compounds were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compounds 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, ki = 62, 12 nM) and 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, ki = 28, 3.3 nM) exhibited high affinities for the 5-HT1A/5-HT7 receptors coupled with potent serotonin reuptake inhibition. Specifically, the most promising compound 21n possessed a good oral pharmacokinetic properties and an acceptable hERG profile, and showed potent antidepressant-like effect in the FST and TST models.
- Gu, Zheng-Song,Zhou, Ai-nan,Xiao, Ying,Zhang, Qing-Wei,Li, Jian-Qi
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p. 701 - 715
(2018/01/03)
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- Efficient Difluoromethylation of Alcohols Using TMSCF2Br as a Unique and Practical Difluorocarbene Reagent under Mild Conditions
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A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF2Br (TMS=trimethylsilyl) as a unique and practical difluorocarbene source is developed. This method allows primary, secondary, and even tertiary alkyl difluoromethyl ethers to be synthesized under weakly basic or acidic conditions. The reaction mainly proceeds through the direct interaction between a neutral alcohol and difluorocarbene, which is different from the difluoromethylation of phenols. Moreover, alcohols containing other moieties that are also reactive toward difluorocarbene can be transformed divergently by using TMSCF2Br. This research not only solves the synthetic problem of difluorocarbene-mediated difluoromethylation of alcohols, it also provides new insights into the different reaction mechanisms of alcohol difluoromethylation and phenol difluoromethylation with difluorocarbene species.
- Xie, Qiqiang,Ni, Chuanfa,Zhang, Rongyi,Li, Lingchun,Rong, Jian,Hu, Jinbo
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supporting information
p. 3206 - 3210
(2017/03/17)
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- OPIOID RECEPTOR MODULATORS
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The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, 0, or S; Y1 is H, -(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alky
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Page/Page column 97; 98
(2016/06/14)
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- Constructing iboga alkaloids via C-H bond functionalization: Examination of the direct and catalytic union of heteroarenes and isoquinuclidine alkenes
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The iboga alkaloids have attracted considerable attention in both the scientific community and popular media due to their reported ability to reverse or markedly diminish cravings for, and self-administration of, the major drugs of abuse. We have developed three new intramolecular C-H functionalization procedures leading to the core seven-membered ring of the iboga skeleton, a cyclization that proved to be highly challenging. The electrophilic palladium salt Pd(CH3CN)4(BF4)2 was effective for the cyclization of diverse N-(2-arylethyl)isoquinuclidines with yields of 10-35%. A two-step, bromination-reductive Heck reaction protocol was also effective for the synthesis of ibogamine in 42% yield. Finally, a direct Ni(0)-catalyzed C-H functionalization provided the benzofuran analogues of ibogamine (74%) and epi-ibogamine (38%). Although each approach suffers from significant shortcomings, in combination, the methods described provide practical routes to diverse ibogamine analogues.
- Kruegel, Andrew C.,Rakshit, Souvik,Li, Xiaoguang,Sames, Dalibor
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p. 2062 - 2071
(2015/10/12)
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- SMALL MOLECULE INDUCERS OF GDNF AS POTENTIAL NEW THERAPEUTICS FOR NEUROPSYCHIATRIC DISORDERS
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The invention provides a compound having the structure (I), wherein A is a substituted or unsubstituted ring; Z is present or absent and when present is (II), wherein n is 0, 1, 2, 3, or 4; Y is -(CR11R12)-, -NH(CR11R12)- or -O(CR11R12)- wherein R11 and R12 are each hydrogen or combine to form a carbonyl; and wherein R1 to R10 are herein as described.
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Page/Page column 101; 102
(2013/03/26)
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- Novel benzofuran derivatives with dual 5-HT1A receptor and serotonin transporter affinity
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Several benzofuran derivatives linked to a 3-indoletetrahydropyridine through an alkyl chain were prepared and evaluated for serotonin transporter and 5-HT1A receptor affinities. Their design, synthesis and structure-activity relationships are described.
- Venkatesan, Aranapakam M.,Dos Santos,Ellingboe, John,Evrard, Deborah A.,Harrison, Boyd L.,Smith, Deborah L.,Scerni, Rosemary,Hornby, Geoffrey A.,Schechter, Lee E.,Andree, Terrence H.
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scheme or table
p. 824 - 827
(2010/06/13)
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- BENZOFURANYL- AND BENZOTHIENYL- PIPERAZINYL QUINOLINES AND METHODS OF THEIR USE
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Benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such compounds are disclosed. Methods of using benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such composition in the treatment and/or prevention of serotonin-related disorders, such as depression and anxiety, are also disclosed. In addition, processes for the preparation of benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives are disclosed.
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Page/Page column 21
(2009/04/24)
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- From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3βinhibitors that suppress proliferation and survival of pancreatic cancer cells
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Recent studies have demonstrated that glycogen synthase kinase 3β (GSK-3β) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl) maleimides, potent GSK-3β inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3β and an enhanced selectivity against cyclin-dependent kinase 2 (CDK-2). Selected GSK-3β inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3β inhibitors 5 and 26 resulted in suppression of GSK-3β activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3β inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.
- Gaisina, Irina N.,Gallier, Franck,Ougolkov, Andrei V.,Kim, Ki H.,Kurome, Toru,Guo, Songpo,Holzle, Denise,Luchini, Doris N.,Blond, Sylvie Y.,Billadeau, Daniel D.,Kozikowski, Alan P.
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experimental part
p. 1853 - 1863
(2009/12/31)
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- 3-BENZOFURANYL-4-INDOLYL MALEIMIDES AS POTENT GSK3 INHIBITORS FOR NEUROGENERATIVE DISORDERS
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Compounds of formula (I): and pharmaceutically acceptable salts, esters and solvates thereof, where variables are defined in the specification, useful generally as inhibitors of protein kinases and particularly useful for inhibition of GSK-3. Pharmaceutically compositions and medicaments containing a compound of the invention are provided. The invention provides methods of treatment of protein kinase-related disease, disorders or conditions. The invention provides methods of treatment of GSK-3-related diseases, disorders or conditions. More specifically, methods of treatment of bipolar disorder, including mania, schizophrenia, stroke, epilepsy, motor neuron disease, cranial or spinal trauma, neurodegenerative disorders, including multiple sclerosis (MS), Alzheimer's disease, Fragile X syndrome, autism, Huntington's disease, Parkinson's
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Page/Page column 61; 66; 96
(2008/12/06)
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- 2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H] quinoline-4-carboxylic acid (PSI-697): Identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists
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P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.
- Kaila, Neelu,Janz, Kristin,Huang, Adrian,Moretto, Alessandro,DeBernardo, Silvano,Bedard, Patricia W.,Tam, Steve,Clerin, Valerie,Keith Jr., James C.,Tsao, Desirée H.H.,Sushkova, Natalia,Shaw, Gray D.,Camphausen, Raymond T.,Schaub, Robert G.,Wang, Qin
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- Structure-based design leads to the identification of lithium mimetics that block mania-like effects in rodents. Possible new GSK-3β therapies for bipolar disorders
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More than two million American adults, or approximately one percent of the population 18 years or older, suffer from bipolar disorder. Current treatments include the so-called "mood stabilizers," lithium and valproic acid. Both are relatively dated drugs that are only partially effective and produce various undesirable side effects including weight gain. Based upon continued efforts to understand the molecular target for lithium, it now appears that specific inhibitors of the enzyme glycogen synthase kinase-3β (GSK-3β) may mimic the therapeutic action of mood stabilizers and might therefore allow for the design of improved drugs for treating patients with bipolar disorder as well as certain neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK-3 enzyme suggest the possible use of such inhibitors as neuroprotective agents. In fact, neuroprotection may contribute to the treatment of mood disorders. The present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective GSK-3β inhibitors. The best ligand in this series (having a Ki value of 4.6 nM against GSK-3β) was studied in a novel mouse model of mania that has recently been validated with several clinically effective mood stabilizers. This study presents the first demonstration of the efficacy of a GSK-3β inhibitor in this mouse model of mania. Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events.
- Kozikowski, Alan P.,Gaisina, Irina N.,Yuan, Hongbin,Petukhov, Pavel A.,Blond, Sylvie Y.,Fedolak, Allison,Caldarone, Barbara,McGonigle, Paul
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p. 8328 - 8332
(2008/02/09)
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- Piperidinyl indole and tetrohydropyridinyl indole derivatives and method of their use
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3-Piperidin-4-yl-1H-indole and 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole derivatives are disclosed. Methods of using the derivatives and compositions containing the derivatives in the prevention and/or treatment of serotonin disorders, such as depression and anxiety, are also disclosed. Additionally, processes for the preparation of 3-piperidin-4-yl-1H-indole and 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole derivatives are disclosed.
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Page/Page column 11
(2010/02/10)
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- BENZOFURANYL-AND BENZOTHIENYL-PIPERAZINYL QUINOLINES AND METHODS OF THEIR USE
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Benzofuranyl-and benzothienyl-piperzinyl quinoline derivatives and compositions containing such compounds are disclosed. Methods of using benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such composition in the treatment and/or prevention of serotonin-related disorders, such as depression and anxiety, are also disclosed. In addition, processes for the preparation of benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives are disclosed.
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- Intramolecular [3 + 2]-cycloaddition reaction of push-pull dipoles across heteroaromatic π-systems
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(Chemical Equation Presented) Push-pull dipoles generated from the Rh(II)-catalyzed reaction of diazo imides containing tethered heteroaromatic rings undergo successful [3 + 2]-cycloaddition across the 2,3-π-bond to provide novel pentacyclic compounds in
- Mejia-Oneto, Jose M.,Padwa, Albert
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p. 3241 - 3244
(2007/10/03)
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- Electrochemical partial fluorination of organic compounds. 74. Efficient anodic synthesis of 2-fluoro- and 2,3-difluoro-2,3-dihydrobenzofuran derivatives
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Anodic fluorination of 3-substituted benzofuran derivatives in a variety of fluoride salts resulted in the formation of three fluorinated products; two stereoisomers of 2,3-difluoro-2,3-dihydrobenzofuran (cis and trans) and cis-2-fluoro-3-hydroxy-2,3-dihydrobenzofuran derivatives. Dehydrofluorination of the main products, cis-difluoro derivatives, furnished the nonaromatic 2-fluoro-3-benzofuranyledene derivatives instead of the aromatic 2-fluorobenzofuran derivatives.
- Dawood, Kamal M.,Fuchigami, Toshio
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p. 5302 - 5306
(2007/10/03)
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- Synthesis of benzofuroquinolizine for α-2 adrenoceptor antagonist MK- 912: An O-analogue of the Pictet-Spengler reaction
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Efficient synthesis of benzofuroquinolizine ketone 1 was accomplished in four steps from ethyl 3-benzofuranacetate. The O-analogue of the Pictet- Spengler cyclization was used to form the benzofuroquinolizine ring structure as a key step.
- Albaneze-Walker,Rossen,Reamer,Volante,Reider
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p. 4917 - 4920
(2007/10/03)
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- Antidepressant 1-arylalkyl-4-(alkoxy pyridinyl)-and 4-(alkoxypyrimidinyl) piperazine derivatives
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Novel compound of formula I and pharmaceutically acceptable salts thereof are useful CNS agents: STR1 wherein X is CH or N; X' is CH or a direct covalent link; Y is CH, CH2 or N; Y' is N, NH, O or S; R1 is H, Br, Cl, F, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, CN, CONH2 or CH3 SO2 NH; n is 2 or 3; R2 is H or C1-4 alkyl; R3 is C1-4 alkoxy; R4 is H, Br, Cl, or F; and Z is CH or N.
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- A convenient synthesis of benzofuran-3-carboxyaldehydes
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The benzofuran-3-acetic acids (3a-c) on treatment with pyridine N-oxide give benzofuran-3-carboxyaldehydes (5a-c) on reduction with NaBH4 in methanol yields naturally occurring benzofuran 6a which is converted into 6b and 6c by the literature method.
- Deshpande, A. R.,Paradkar, M. V.
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p. 526 - 528
(2007/10/02)
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- Vinylindenes and Some Heteroanalogues in the Diels-Alder Reaction. IX. 3-Vinylbenzofuran and 1,4-Naphthoquinone
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3-Vinylbenzofuran and 1,4-naphthoquinone react to give r-5a,6,c-12a,c,12b-tetrahydroanthrabenzofuran-5,13-quinone.This adduct undergoes ring opening to 2-(2-hydroxyphenyl)anthraquinone with base and oxygen, but shows no rearrangement to anthrabenzofuran-5,13-quinone.
- Pearson, James R.,Porter, Quentin N.
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p. 907 - 917
(2007/10/02)
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- Reaction of 4-Haloacetoacetate with Phenols in the Presence of Aluminium Chloride
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Reaction of ethyl 4-bromoacetoacetate (1) with phenol in the presence of aluminium chloride gave ethyl 4-bromo-3-hydroxy-3-(2-hydroxyphenyl)butyrate (3a), which can be regarded as an intermediate of the Pechmann reaction.Similar reaction of ethyl 4-chloroacetoacetate (7) with phenol in the presence of aluminium chloride gave the 4-chloro derivative 8a.Compound 3a was treated with either hydrogen chloride in ethanol or triethylamine followed by treatment with p-toluenesulfonic acid to give 4-bromomethylcoumarin (4a) or ethyl 3-benzofuranacetate (6a), respectively.Similarly, reactions of phenol derivatives 2 with 1 gave the corresponding 3-hydroxybutyrates 3, which were transformed to the coumarins 4 and the 3-benzofuranacetates 6.
- Kimura, Hitoshi,Sato, Hirotoshi,Tsuchiya, Chizuko,Chiba, Takuo,Kato, Tetsuzo
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p. 552 - 558
(2007/10/02)
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