- Synthesis and structure–activity relationships of novel arylpiperazines as potent antagonists of α1-adrenoceptor
-
Arylpiperazines 2–11 were synthesized, and their biological profiles at α1-adrenergic receptors (α1-ARs) assessed by binding assays in CHO cells expressing human cloned subtypes and by functional experiments in isolated rat vas deferens (α1A), spleen (α1B
- Silva, Renata Oliveira,de Oliveira, Andressa Souza,Nunes Lemes, Laís Flávia,de Camargo Nascente, Luciana,Coelho do Nascimento Nogueira, Patrícia,Silveira, Edilberto R.,Brand, Guilherme D.,Vistoli, Giulio,Cilia, Antonio,Poggesi, Elena,Buccioni, Michela,Marucci, Gabriella,Bolognesi, Maria Laura,Romeiro, Luiz Antonio Soares
-
-
Read Online
- A simple, efficient access to functionalized pyrrolobenzazepines related to the BBC core of cephalotaxine
-
Tetracyclic nitrile 19a and ester 19b, exhibiting the ABC core of cephalotaxine 1a, were prepared through K-H-induced cyclization of thioimides 14a and 14b, respectively. This new ring-closure methodology proved to he particularly efficient: thus nitrile 19a was obtained in only 7 steps with a 17 % overall yield from commercially available, inexpensive safrole 2.
- De Oliveira, Eduardo R.,Dumas, Francoise,D'Angelo, Jean
-
-
Read Online
- An unexpected pentacarbonyl chromium complexation of a cyano group of the ABC core of cephalotaxine
-
A new penta-carbonyl chromium(0) complex of the type [Cr(CO)5(L)] (L = tetracyclic pyrrolobenzazepine unit 3) was surprisingly obtained by reacting [Cr(CO)3(naphthalene)] or [Cr(CO)3(tmtach)] with the tetracyclic pyrrolobenzazepine unit 3 in octane-ether/THF-solvent mixtures or acetone under ambient temperature or reflux. The new complex 13 has been characterized by spectral analysis including IR, 1H and 13C NMR data. For comparison purposes, the safrole-tricarbonyl chromium(0) complex 12 was prepared and characterized. X-ray diffraction analyses of both complexes were determined. Based on the above data, an octahedral structure has been assigned to the new complex 13.
- Quteishat, Laith,Panossian, Armen,Le Bideau, Franck,Alsalim, Rana,Retailleau, Pascal,Troufflard, Claire,Rose, Eric,Dumas, Fran?oise
-
-
Read Online
- Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents
-
The necessity for developing novel cytostatic agents with improved activities and reduced side-effects to tackle cancer prompted us to investigate mitochondria-targeted compounds, an approach that is gaining attention for the selective transportation of cytotoxic agents. We envisioned the possibility of conjugating a phenethyl alcohol motif, decorated with a series of phenol-based substituents on the aryl moiety, with a triphenyl phosphonium scaffold (a mitochondria-directed vector), through a hydrocarbon chain of different lengths. Thus, such compounds that incorporate the phenethyl skeleton can be considered as masked phenolic compounds derived from relevant natural counterparts found in olive tree (e.g. tyrosol, hydroxytyrosol). Title compounds exhibited very strong in vitro antiproliferative activities against the panel of six human tumor cell lines tested, with GI50 values ranging from the nanomolar (0.026 ± 0.010 μM for 36) to the submicromolar range in most of the cases; this represents an improvement of up to 350-fold compared to classical chemotherapeutic agents, like 5-fluorouracil or cisplatin. Interestingly, decrease in the linker length led to an increase of GI50 values against non-tumor cells, thus allowing a remarkable improvement of selectivity (SI up to 269). The very promising antiproliferative activities prompted us to further investigate their behaviour against multidrug resistant cell lines (MDR). The results indicated a reduced sensitivity of the multidrug resistant cells to compounds, probably due to P-gp-mediated efflux of these antiproliferative agents. Interestingly, activities were completely restored to the same levels by co-administration of tariquidar, a well-known inhibitor of P-gp. Flow cytometry analysis on sensitive cell lines revealed a decrease in the percentage of cells in G1 phase accompanied by increase in S and G2/M phases. In addition, a significant increase in subG1 area, was observed. These results are compatible with the necrotic and apoptotic cell death detected in the Annexin V assay, and with the depolarization of the mitochondria membrane. Thus, the new mitochondriotropic agents reported herein can be considered as promising antiproliferative agents, endowed with remarkable potency and selectivity, including MDR cells, upon co-administration with a pump-efflux inhibitor.
- Hicke, Francisco J.,Puerta, Adrián,Dini?, Jelena,Pe?i?, Milica,Padrón, José M.,López, óscar,Fernández-Bola?os, José G.
-
-
- Tuning the activity of iminosugars: novel N-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors
-
We have designed unprecedented cholinesterase inhibitors based on 1-deoxynojirimycin as potential anti-Alzheimer’s agents. Compounds are comprised of three key structural motifs: the iminosugar, for interaction with cholinesterase catalytic anionic site (
- Ahuja-Casarín, Ana I.,Merino-Montiel, Penélope,Vega-Baez, José Luis,Montiel-Smith, Sara,Fernandes, Miguel X.,Lagunes, Irene,Maya, Inés,Padrón, José M.,López, óscar,Fernández-Bola?os, José G.
-
p. 138 - 146
(2020/11/27)
-
- Process for preparing hydroxytyrosol
-
The invention discloses a process for preparing hydroxytyrosol. According to the process, benzodioxole is used as a starting material, firstly, benzodioxole and ethylene oxide are subjected to a Friedel-Crafts alkylation reaction to prepare pepper ethanol, and then the pepper ethanol is subjected to a catalytic hydrolysis reaction to prepare hydroxytyrosol. The hydroxytyrosol preparation process disclosed by the invention has the characteristics of easily available and cheap raw materials, simple operation process, safety, environmental protection and the like.
- -
-
Paragraph 0050; 0075-0089
(2021/08/19)
-
- The total synthesis of berberine and selected analogues, and their evaluation as amyloid beta aggregation inhibitors
-
The total synthesis of berberine and selected analogues. And their evaluation as amyloid β (Aβ) aggregation inhibitors is described. The key step in the synthesis, the assembly of the berberine framework, was accomplished using an intermolecular Heck reaction. Berberine analog 17 incorporating a tertiary amine moiety showed good anti Aβ aggregation activity, water solubility, and almost no toxicity to nerve cells.
- Tajiri, Misato,Yamada, Ryo,Hotsumi, Mayumi,Makabe, Koki,Konno, Hiroyuki
-
-
- Nickel-Catalyzed Electrochemical Reductive Relay Cross-Coupling of Alkyl Halides to Aryl Halides
-
A highly regioselective Ni-catalyzed electrochemical reductive relay cross-coupling between an aryl halide and an alkyl halide has been developed in an undivided cell. Various functional groups are tolerated under these mild reaction conditions, which pro
- Fang, Ping,Jiao, Ke-Jin,Liu, Dong,Ma, Hong-Xing,Mei, Tian-Sheng,Qiu, Hui
-
supporting information
p. 6520 - 6524
(2020/01/24)
-
- Development of Pd(OAc)2-catalyzed tandem oxidation of C[sbnd]N, C[sbnd]C, and C(sp3)–H bonds: Concise synthesis of 1-aroylisoquinoline, oxoaporphine, and 8-oxyprotoberberine alkaloids
-
A catalytic tandem oxidation of C[sbnd]N, C[sbnd]C, and C(sp3)–H bonds is developed. This tandem oxidation is applied to two-step total syntheses of papaveraldine and pulcheotine A. Additionally, the total synthesis of liriodenine is achieved in six steps from homopiperonyl alcohol and 2-bromophenylacetonitrile by applying this catalytic tandem oxidation. Moreover, the direct conversion of xylopinine to 8-oxypseudopalmatine in a 76% yield demonstrates the versatility of this catalytic reaction.
- Nishimoto, Saeko,Nakahashi, Hiromichi,Toyota, Masahiro
-
supporting information
(2020/11/13)
-
- Ytterbium-Catalyzed Intramolecular [3 + 2] Cycloaddition based on Furan Dearomatization to Construct Fused Triazoles
-
The 1,2,3-triazole-containing polycyclic architecture widely exists in a broad spectrum of synthetic bioactive molecules, and the development of expeditious methods to synthesize these skeletons remains a challenging task. In this work, the catalytic cyclization of biomass-derived 2-furylcarbinols with an azide to form fused triazoles is described. This approach takes advantage of a single catalyst Yb(OTf)3 and operates via a furfuryl-cation-induced intramolecular [3 + 2] cycloaddition/furan ring-opening cascade.
- Xu, Xiaoming,Zhong, Ying,Xing, Qingzhao,Gao, Ziwei,Gou, Jing,Yu, Binxun
-
supporting information
p. 5176 - 5181
(2020/07/14)
-
- Structure-Activity Relationship Study Enables the Discovery of a Novel Berberine Analogue as the RXRα Activator to Inhibit Colon Cancer
-
We reported recently that berberine (Ber), a traditional oriental medicine to treat gastroenteritis, binds and activates retinoid X receptor α (RXRα) for suppressing the growth of colon cancer cells. Here, we extended our studies based on the binding mode of Ber with RXRα by design, synthesis, and biological evaluation of a focused library of 15 novel Ber analogues. Among them, 3,9-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride (B-12) was identified as the optimal RXRα activator. More efficiently than Ber, B-12 bound and altered the conformation of RXRα/LBD, thereby suppressing the Wnt/β-catenin pathway and colon cancer cell growth via RXRα mediation. In addition, B-12 not only preserved Ber's tumor selectivity but also greatly improved its bioavailability. Remarkably, in mice, B-12 did not show obvious side effects including hypertriglyceridemia as other RXRα agonists or induce hepatorenal toxicity. Together, our study describes an approach for the rational design of Ber-derived RXRα activators as novel effective antineoplastic agents for colon cancer.
- Xu, Beibei,Jiang, Xunjin,Xiong, Jing,Lan, Jun,Tian, Yuan,Zhong, Linhai,Wang, Xinquan,Xu, Ning,Cao, Hanwei,Zhang, Wenqing,Zhang, Hao,Hong, Xiaoting,Zhan, Yan-Yan,Zhang, Yandong,Hu, Tianhui
-
p. 5841 - 5855
(2020/07/03)
-
- Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C-N and C-O Bond Formation
-
A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N-or O-arylation step leading to indolines, dihydrobenzofurans, and six-membered analogues. The general applicability and functional group tolerance of this method were exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process.
- Henry, Martyn C.,Senn, Hans Martin,Sutherland, Andrew
-
p. 346 - 364
(2019/01/08)
-
- COMPOUNDS AND COMPOSITIONS AND USES THEREOF
-
Disclosed are compounds of formula (I): and pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disease and disorders in a subject in need are also disclosed.
- -
-
Paragraph 0281-0283; 0502-0504
(2018/02/28)
-
- PLANT GROWTH-PROMOTION AGENT AND METHOD FOR PROMOTING PLANT GROWTH
-
The present invention concerns: a plant growth-promoting agent comprising a compound represented by Formula (I) or a salt thereof: wherein Ar1 represents a substituted or unsubstituted phenyl group, NZ represents a nitrogen-containing heterocyclic ring group or an acyclic nitrogen-containing group having a partial structure of the nitrogen-containing heterocyclic ring group, n is 0, 1, or 2, R1 and R2 each represent a hydrogen atom, a substituted or unsubstituted C1-3-alkyl group, a cyano group, or a carboxyl group, R1 and R2 may together form an oxo group, and when n is 2, R1 or R2 may be the same or different; and a method for promoting plant growth using the plant growth-promoting agent.
- -
-
Paragraph 0130; 0131
(2017/11/11)
-
- Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
-
Trypanosomiasis and leishmaniasis keep being a real challenge for health and development of African countries. Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR) and hydroxytyrosol (HT) and several of their esters and metabolites. We found significant IC50 values against Trypanosoma brucei for HT decanoate ester and HT dodecanoate ester (0.6 and 0.36 μM, respectively). This represents a large increase in activity with respect to HT (79 and 132 fold, respectively). Moreover, both compounds displayed a high selectivity index against MRC-5, a non-tumoral human cell line (118 and 106, respectively). Then, we synthesized a focused library of compounds to explore structure-activity. We found the ether and thiourea analogs of HT decanoate ester and HT dodecanoate ester also showed IC50 values against T. brucei in the low micromolar range. In conclusion, the di-ortho phenolic ring and medium size alkyl chain are essential for activity whereas the nature of the chemical bond among them seems less important.
- Belmonte-Reche, Efres,Martínez-García, Marta,Pe?alver, Pablo,Gómez-Pérez, Verónica,Lucas, Ricardo,Gamarro, Francisco,Pérez-Victoria, José María,Morales, Juan Carlos
-
p. 132 - 140
(2016/05/24)
-
- Catalytic Cyclization of o-Alkynyl Phenethylamines via Osmacyclopropene Intermediates: Direct Access to Dopaminergic 3-Benzazepines
-
A novel osmium-catalyzed cyclization of o-alkynyl phenethylamines to give 3-benzazepines is reported. The procedure allows the straightforward preparation of a broad range of dopaminergic 3-benzazepine derivatives. Mechanistic investigations revealed that the process takes place via osmacyclopropene intermediates, which were isolated and characterized by X-ray crystallography.
- álvarez-Pérez, Andrea,González-Rodríguez, Carlos,García-Yebra, Cristina,Varela, Jesús A.,O?ate, Enrique,Esteruelas, Miguel A.,Saá, Carlos
-
supporting information
p. 13357 - 13361
(2015/11/09)
-
- A versatile total synthesis of 8-oxyberberine and oxohomoberberines
-
The total syntheses of 8-oxyberberine and oxohomoberberines were accomplished starting from commercially available 5-bromobenzo[d][1,3]dioxole, piperonal and sesamol in high total yield. The key steps involved a modified Pomeranz-Fritsch reaction and the intramolecular Heck cyclization. This approach is short, convenient and suitable for the preparation of homoberberine analogues.
- He, Yun,Zheng, Yang,Hai, Li,Wu, Yong
-
p. 1121 - 1127
(2015/01/16)
-
- SANGUINARINE ANALOG PP2C INHIBITORS FOR CANCER TREATMENT
-
Sanguinarine analogs as PP2C inhibitors are disclosed for the treatment of various cancers, as well as methods of synthesizing such analogs.
- -
-
Page/Page column 65
(2014/10/03)
-
- Short and efficient syntheses of protoberberine alkaloids using palladium-catalyzed enolate arylation
-
A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladiumcatalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50%is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here.
- Gatland, Alice E.,Pilgrim, Ben S.,Procopiou, Panayiotis A.,Donohoe, Timothy J.
-
supporting information
p. 14555 - 14558
(2015/02/19)
-
- Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-Adrenergic receptor blocking properties
-
We described herein the discovery of 1-(2-(benzo[d] [1,3]dioxol-6-yl)ethyl) -4-(2-methoxyphenyl) piperazine (LASSBio-772), as a novel potent and selective alpha 1A/1D adrenoceptor (AR) antagonist selected after screening of functionalized N-phenylpiperazine derivatives in phenylephrine-induced vasoconstriction of rabbit aorta rings. The affinity of LASSBio-772 for alpha 1A and alpha 1B AR subtypes was determined through displacement of [ 3H]prazosin binding. We obtained Ki values of 0.14 nM for the alpha 1A-AR, similar to that displayed by tamsulosin (Ki = 0.13 nM) and 5.55 nM for the alpha 1B-AR, representing a 40-fold higher affinity for alpha 1A-AR. LASSBio-772 also presented high affinity (KB = 0.025 nM) for the alpha 1D-AR subtype in the functional rat aorta assay, showing to be equipotent to tamsulosin (KB = 0.017 nM).
- Romeiro, Luiz A.S.,Da Silva Ferreira, Marcos,Da Silva, Leandro L.,Castro, Helena C.,Miranda, Ana L.P.,Silva, Cláudia L.M.,No?l, Franois,Nascimento, Jéssica B.,Araújo, Claudia V.,Tibiri?á, Eduardo,Barreiro, Eliezer J.,Fraga, Carlos A.M.
-
scheme or table
p. 3000 - 3012
(2011/07/08)
-
- Synthesis of alkaloids of Galipea officinalis by alkylation of an α-amino nitrile
-
A new synthetic approach directed towards the synthesis of naturally occurring 2-alkyl-tetrahydroquinolines is described. The C-C bonds in the α position relative to the nitrogen atom were formed by the reversal of the polarity of the C=N bond of α-amino nitrile 6, which was prepared electrochemically from 1-(phenylethyl)-tetrahydroquinoline. A NaBH 4-mediated reductive decyanation process furnished benzylic amines 16a-d as mixtures of diastereomers (50-60% de). The catalytic hydrogenolysis of these amines was performed in the presence of Pearlman's catalyst to give the tetrahydroquinolines 17a-d in yields ranging from 70% to 95%. Methylation of the free nitrogen atom afforded the title compounds 1-4 in 70-90% yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Shahane, Saurabh,Louafi, Fadila,Moreau, Julie,Hurvois, Jean-Pierre,Renaud, Jean-Luc,Van De Weghe, Pierre,Roisnel, Thierry
-
experimental part
p. 4622 - 4631
(2009/05/07)
-
- 4-(CONDENSED CYCLICMETHYL)-IMIDAZOLE-2-THIONES ACTING AS ALPHA2 ADRENERGIC AGONISTS
-
Compounds of Formula 1 where the variables have the meaning defined in the specification are agonists of alpha2 adrenergic receptors. Several compounds of the disclosure are specific or selective to alpha 2B and/or alpha2C adrenergic receptors in preferen
- -
-
Page/Page column 22-23
(2008/06/13)
-
- Novel α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonists of 2,3-benzodiazepine type: Chemical synthesis, in vitro characterization, and in vivo prevention of acute neurodegeneration
-
Under pathophysiological conditions, α-amino-3-hydroxy-5-methyl-4- isoxazole propionate (AMPA) receptor activation is considered to play a key role in several disorders of the central nervous system. In the search for AMPA receptor antagonists, the synthe
- Elger, Bernd,Huth, Andreas,Neuhaus, Roland,Ottow, Eckard,Schneider, Herbert,Seilheimer, Bernd,Turski, Lechoslaw
-
p. 4618 - 4627
(2007/10/03)
-
- Conformational analysis: Crystallographic, NMR, and molecular mechanics studies of flexible sulfonic esters
-
Two novel X-ray structures of the sulfonic ester derivatives 2-(6-iodo-1,3-benzodioxol-5-yl)ethyl 4-nitrobenzenesulfonate, 3, and 2-(6-iodo-1,3 -benzodioxol-5-yl)ethyl 4-methylbenzenesulfonate, 4, have been obtained in a study aimed at analyzing the struc
- Munro, Orde Q.,McKenzie, Jean M.,Strydom, Sandra D.,Gravestock, David
-
p. 2448 - 2459
(2007/10/03)
-
- Spiro cyclisations of N-acyliminium ions involving an aromatic π-nucleophile
-
Spiro 2-pyrrolidin-5-ones were obtained from N-substituted succinimides by a two-step procedure, involving 5- or 6-endo-trig cyclisation of N-acyliminium ion intermediates with a tethered aromatic π-nucleophile.
- Bailey, Patrick D.,Morgan, Keith M.,Smith, David I.,Vernon, John M.
-
p. 3369 - 3378
(2007/10/03)
-
- N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
-
Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
- -
-
Page column 121
(2010/01/30)
-
- Sulfonamides for treatment of endothelin-mediated disorders
-
Thienylsulfonamides and their pharmaceutically acceptable derivatives, pharmaceutical compositions, articles of manufacture, combinations, lyophilized powders and methods for the treatment of endothelin diseases using these formulations and sulfonamides a
- -
-
-
- Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
-
Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
- -
-
-
- Sulfonamides for treatment of endothelin-mediated disorders
-
Thienyl-, furyl- and pyrrolyl-sulfonamides, pharmaceutically-acceptable salts of sulfonamides, formulations of salts and the sulfonamides, and methods for modulating or altering the activity of the endothelin family of peptides using the formulations and
- -
-
-
- Formulation of sulfonamides for treatment of endothelin-mediated disorders
-
Formulations of pharmaceutically-acceptable salts of thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides using the formulations are provided. In particular, formulations of so
- -
-
-
- A new method for the synthesis of α-thio aldehydes and alcohols from aldehydes with one-carbon elongation
-
A two-step and high-yield method for the synthesis of α-thio aldehydes from aldehydes with one-carbon elongation is realized by using chloromethyl phenyl sulfoxide as a one-carbon homologating agent. The α-thio aldehydes are easily converted to desulfurized alcohols with Bu3SnH and AIBN in refluxing benzene in good yield. (C) 2000 Elsevier Science Ltd.
- Satoh, Tsuyoshi,Kubota, Ko-Ichi
-
p. 2121 - 2124
(2007/10/03)
-
- Catalytic generation and trapping of acylmetals containing Ni and Cu with enolates
-
Carbonylative cyclization of iodoarenes and iodoalkenes containing a proximal enolate precursor can selectively provide either cyclic ketones or lactones in the presence of Ni or Cu catalysts via trapping of putative acylmetal derivatives with C- or O-enolates, respectively; the ring size and regioselectivity of the reaction may be predicted based on two generalizations derived from the recently developed corresponding Pd-catalyzed reaction.
- Negishi, Ei-ichi,Makabe, Hidefumi,Shimoyama, Izumi,Wu, Guangzhong,Zhang, Yantao
-
p. 1095 - 1106
(2007/10/03)
-
- Intramolecular 1,3-dipolar cycloaddition as a tool for the preparation of azaspirocyclic keto aziridines. Synthesis of intermediates for the total synthesis of (±) (±)-cephalotaxine
-
The thermal intramolecular azide-enone 1,3-dipolar cycloaddition to azaspirocyclic keto aziridines 17 and 18 is reported. α-Hydroxylation and oxidation to the corresponding diketo aziridine 2 provided an intermediate in a synthetic approach toward cephalo
- Molander, Gary A.,Hiersemann, Martin
-
p. 4347 - 4350
(2007/10/03)
-
- MUSCARINIC RECEPTOR ANTAGONISTS
-
The invetion is a method of treating irritable bowel syndrome with a compound selected from the formula STR1 wherein R, R 1, m, n p are as defined in the specification, or a pharmaceutically acceptable salt thereof.
- -
-
-
- BENZOPYRANES AS POTASSIUM CHANNEL OPENERS
-
The present invention relates to compounds of formula (I) and the pharmaceutically acceptable salts thereof, wherein the dashed line represents an optional covalent bond; X is O, NH, S or a direct link; R. sup.3 is hydroxy when the dashed line does not represent a covalent bond and R 3 is absent when the dashed line represents a covalent bond; R. sup.4 is (a), when X is O, a group of formula (i), (b), when X is O, NH or S, optionally substituted hydroxyphenyl, (c) an optionally substituted 4-to 7-membered heterocyclic ring, or (d), when X is NH, a group of formula (ii). The compounds are useful for the treatment of disease associated with the altered tone or motility of smooth muscle. STR1
- -
-
-
- ANTICHOLINERGIC AGENTS
-
Selective muscarinic receptor antagonists of formula (I): STR1 wherein R 1 and R 2 are both optionally substituted phenyl, the broken line is an optional bond, X is > COH--, > SiOH--or CH--when the double bond is absent or is > C= when the double bond is present, X being attached to a carbon atom of A, A is selected from certain piperidine and pyrrolidine groups, n is 1 to 3 and R 3 is optionally substituted phenyl or thienyl, pyridyl or pyrazinyl.
- -
-
-
- Certain 1-azabicyclo[2.2.1]heptanes useful as muscarinic receptor antagonists
-
MUSCARINIC RECEPTOR ANTAGONISTS OF THE FOLLOWING FORMULAE: STR1 Muscarinic receptor antagonists, useful especially in the treatment of irritable bowel syndrome, of formula (IA) or (IB) or a pharmaceutically acceptable salt thereof, where R 2 and R 3 are each independently H, halo or C 1 -C 4 alkyl; m is 0, 1 or 2; n is 1, 2 or 3; Y is a direct link, O or S; with the proviso that when n is 1, Y is a direct link; Het is a group of formula (A) or (B), where p is 0, 1 or 2, q is 1, 2 or 3, and r is 0, 1, 2 or 3, with the proviso that the sum of p, q and r is at least 3, the N atom of ""Het"" being attached to the group (CH 2) n in formula (IA) and to the H atom in formula (IB); and R 1 is a group of formula (a), (b) or Het 1, where R 4 and R 5 are each independently H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, --(CH 2) t OH, halo, trifluoromethyl, cyano, --(CH 2) t NR 6 R 7, --CO(C 1 -C 4 alkyl), --OCO(C 1 -C 4 alkyl), CH(OH)(C 1 -C 4 alkyl), --C(OH)(C 1 -C 4 alkyl) 2, --SO 2 NH 2, --(CH 2) t CONR 6 R 7 or --(CH 2) t COO(C 1 -C 4 alkyl); R 6 and R 7 are each independently H or C 1 -C 4 alkyl; t is 0, 1 or 2; X and X 1 are each independently O or CH 2 ; s is 1, 2 or 3; and Het 1 is pyridyl, pyrazinyl or thienyl.
- -
-
-
- Piperidine and pyrrolidine derivatives
-
According to the invention there is provided a compound of formula (I): R 1 --O(CH 2) m A(CH 2) n XR or a pharmaceutically acceptable salt thereof, wherein R 1 is a group of formula (a or b) where Z is --(CH 2) 2-, --CH CH--, --CH 2 --S-- or --CH 2 --O--;
- -
-
-
- Synthesis and LTB4 receptor antagonist activities of the naturally occurring LTB4 receptor antagonist Leucettamine A and related analogues
-
The isolation and structure determination of the naturally occurring LTB4 receptor antagonist Leucettamine A (1) was recently reported. Herein we describe the synthesis of this natural product, the preparation of several analogues, and their effectiveness as antagonists of [3H]LTB4 binding to intact human U-937 cells. Total synthesis of Leucettamine A (1) is achieved by a convergent route which takes advantage of the elements of symmetry within the molecule. Syntheses of analogues of 1, which lacked the same degree of symmetry, are achieved by a different approach starting from α- amino acids. The natural product 1 inhibits [3H]LTB4 binding to its receptors on intact human U-937 cells with a K(i) = 3.5 ± 0.8 μM and is devoid of measurable agonist activity at the concentrations tested. 2-Amino imidazole analogues of 1 lacking the dioxolane groups were prepared. Generally these are significantly less potent than 1. However, one (26), designed on the basis of a putative structural overlay with LTB4, demonstrated potency comparable to that of the natural product (K(i) = 2.4 ± 0.2 μM).
- Boehm,Gleason,Pendrak,Sarau,Schmidt,Foley,Kingsbury
-
p. 3333 - 3340
(2007/10/02)
-
- Certain amines which are muscarinic receptor antagonists
-
Amines of the following formula: STR1 where the variables are defined in the specification are useful in the treatment of diseases associated with altered motility and/or tone of smooth muscle.
- -
-
-
- Muscarinic receptor antagonists
-
Compounds of the formula I STR1 wherein X, Y and v are as defined below, novel intermediates used in their synthesis, and the pharmaceutically acceptable salts of such compounds and intermediates. The compounds of formula I and the novel intermediates used in their synthesis are muscarinic receptor antagonists that are selected for smooth muscle muscarinic sites and are useful in the prevention and treatment of diseases associated with altered motility or tone of smooth muscle, such as irritable bowel syndrome, diverticular disease, urinary incontinence, aesophageal achalasia, and chronic obstructive airways disease.
- -
-
-
- 1-ARYLETHYL-3-SUBSTITUTED PIPERIDINES
-
A series of novel 1-(phenethyl) and 1-(1-heteroarylethyl)-3-substituted piperidine derivatives have been prepared, including their pharmaceutically acceptable salts and various novel key intermediates therefor. The 3-substituent present in these compounds is an unsubstituted or substituted diphenylmethoxy group or a diphenylmethoxy-derived group, while the 1-substituent is unsubstituted or substituted phenethyl or 1-(2-heteroarylethyl) wherein the heteroaryl moiety is thienyl, pyridyl or pyrazinyl. These compounds in the form of both their racemates and 3R-isomers, are useful in therapy as smooth muscle muscarinic receptor antagonists and therefore, are of value in the treatment diseases associated with altered motility and/or smooth muscle tone. The most preferred compound is (3R)-diphenylmethoxy-1-(3,4-methylenedioxyphenethyl)piperidine. Methods for preparing these compounds from known starting materials are provided.
- -
-
-
- PYRROLIDINE DERIVATIVES
-
Compounds of the formula STR1 wherein R, Y and R 1 are as defined in the specification. These compounds are muscarinic receptor antagonists which are selective for smooth muscle muscarinic sites over cardiac muscarinic sites, and are useful in the treatment of diseases associated with altered motility on tone of smooth muscle, including irritable bowel syndrome, diverticular disease, urinary incontinence, oesophageal achalasia and chronic obstructive airways disease.
- -
-
-
- Muscarinic receptor antagonists
-
A compound of the formula (IA) or (IB), useful in treating diseases associated with the altered motility and/or tone of smooth muscle, such as irritable bowel syndrome, of the formula:- and their pharmaceutically-acceptable salts, where Y is-CH?CH?-,-CH=CH-,-CH?-S-,-CH?-O-,-O-or-S-; and X is a group of the formula:- wherein m is 1 or 2; R1 and R2 are each independently H or C?-C? alkyl or together represent-(CH?)n-where n is an integer of from 2 to 5; R3 is H or C?-C? alkyl; Z is a direct link,-CH?-,-(CH? )?-,-CH?O-or-CH?S-; and R? is pyridyl, pyrazinyl, thienyl or a group of the formula:- where either R? and R? are each independently selected from H, C?-C? alkyl, C?-C? alkoxy, halo,-CF?,-CN,-(CH?) pNR? R?,-OCO(C?-C? alkyl),-CO(C?-C? alkyl),-CH(OH)(C?-C? alkyl),-C(OH) (C?-C? alkyl)?,-SO?NH?,-NHSO?(C?-C? alkyl),-(CH?)pOH,-(CH?)p COO(C?-C? alkyl),-(CH?)pCONR? R?, or R? and R? together represent-(CH?)q-,-O(CH?) rO-or-O(CH? )t-where in the latter the oxygen atom is attached to the 3-or 4-position of the benzene ring; R? and R? are each independently H or C?-C? alkyl; p is 0, 1 or 2; q is 3, 4 or 5; r is 1, 2 or 3; and t is 2, 3 or 4.
- -
-
-