- Transient Kinetics and Quantum Yield Studies of Nanocrystalline α-Phenyl-Substituted Ketones: Sorting Out Reactions from Singlet and Triplet Excited States
-
Recent work has shown that diarylmethyl radicals generated by pulsed laser excitation in nanocrystalline (NC) suspensions of tetraarylacetones constitute a valuable probe for the detailed mechanistic analysis of the solid-state photodecarbonylation reaction. Using a combination of reaction quantum yields and laser flash photolysis in nanocrystalline suspensions of ketones with different substituents on one of the α-carbons, we are able to suggest with confidence that a significant fraction of the initial α-cleavage reaction takes place from the ketone singlet excited state, that the originally formed diarylmethyl-acyl radical pair loses CO in the crystal with time constants in the sub-nanosecond regime, and that the secondary bis(diarylmethyl) triplet radical pair has a lifetime limited by the rate of intersystem crossing of ca. 70 ns.
- Park, Jin H.,Chung, Tim S.,Hipwell, Vince M.,Rivera, Edris,Garcia-Garibay, Miguel A.
-
-
Read Online
- Ruthenium-catalysed one-pot regio- and diastereoselective synthesis of pyrrolo[1,2-a] indoles via cascade C-H functionalization/annulation
-
A cascade approach has been developed towards dual C-C bond formation via consecutive C-H functionalization/cyclization giving access to pyrrolo[1,2-a]indoles in a highly regio- and diastereoselective manner using catalytic [Ru(p-cymene)Cl2]2. The methodology was further expanded to attain pentacyclic structures involving manifold C-C bond creation.
- Singh, Sukhdev,Butani, Himanshu H.,Vachhani, Dipak D.,Shah, Anamik,Van Der Eycken, Erik V.
-
-
Read Online
- Pharmacological studies and synthesis of morpholino alkyl derivatives
-
Seven morpholin derivatives were synthesized (compounds 1-7) and their behavioural effects were evaluated; the elements considered were locomotor activity, motor coordination, catalepsy, stereotyped behaviour and antinociception. All the compounds, at doses of 10-20-40 mg/kg/i.p., induced a reduction of all behavioural elements without a significant antinociceptive effect. These results indicate that these morpholin derivatives affect the central nervous system.
- Saturnino, Carmela,Capasso, Anna,Lancelot, Jean-Chanles,Rault, Sylvain,Buonerba, Mariafrancesca,De Martino, Giovanni
-
-
Read Online
- Triphenylacetic acid amides: Molecular propellers with induced chirality
-
The combination of electronic circular dichroism spectroscopy (ECD), X-ray diffraction, and theoretical calculations permitted a detailed description of an unexpected chirality transfer in triphenylacetamides, which is achieved solely through weak intramolecular interactions. The observed phenomenon proceeds as a cascade process. The triphenylacetamide chromophore is sensitive to even small changes in the relative size of the substituent attached to the stereogenic center. Substitution at the stereogenic center influences helicity of the distal trityl chromophore but does not affect its propeller shape. Deformation of the propeller shape and consequent loss of its C3 symmetry results mainly from substitution of the amide hydrogen and is connected with an increase in steric hindrance. As an outcome of our studies, a model of optical activity of chiral triphenylacetamides is proposed. The performed X-ray studies revealed that this novel class of chiral compounds is likely to be of additional value due to the porosity of the crystals.
- Prusinowska, Natalia,Bendziska-Berus, Wioletta,Jelecki, Maciej,Rychlewska, Urszula,Kwit, Marcin
-
-
Read Online
- RECEPTOR INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING SAME, AND USE THEREOF
-
The present invention discloses a receptor inhibitor of formula (I), a pharmaceutical composition comprising the same and the use thereof.
- -
-
Paragraph 0137; 0145; 0148-0149
(2021/01/28)
-
- Design and synthesis of novel N-[3-(benzimidazol-2-ylamino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives as potential anticancer agents
-
In this contribution, we report the design, synthesis and cytotoxicity studies of a series of N-[3-(benzimidazol-2-yl-amino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives. In vitro cytotoxicity assay of 26 selected compounds was carried out at National Cancer Institute (NCI), USA. Out of them, compounds 10e (NSC D-762842/1) and 11s (NSC D-764942/1) have shown remarkable cytotoxicity with GI50 values ranging between “0.589–14.3?μM” and “0.276–12.3?μM,” respectively, in the representative nine subpanels of human tumor cell lines. Further, flow cytometry analysis demonstrated that compound 10e exerted cell cycle arrest at G2/M phase and showed dose-dependent enhancement in apoptosis in K-562 leukemia cancer cells.
- Kumar, Honnavalli Yogish,Murumkar, Prashant R.,Pawar, Vijay,Srinivasan, B. P.,Yadav, M. R.
-
-
- Catalytic C-C coupling of diazo compounds with arylboronic acids: Using surface modified sewage sludge as catalyst
-
A green, mild and efficient synthesis of diarylmethines using sewage sludge-derived carbonaceous materials (SW) by perchloric acid catalyzed coupling reactions between diazo compounds and arylboronic acids was developed. The reaction shows a high level of functional tolerance and a broad substrate scope. Furthermore, the highly selective 1,2-alkyl shift products were furnished through the sterically demanding R4, R5 migration of diazo compounds (3-diazochromanone). The structures of 1,2-shift products have been further confirmed by single-crystal X-ray analysis. Significantly, the synthesis of the core structures of darifenacin (a clinical drug for overactive bladder syndrome, OAB) and diclofensine (a stimulant drug showing antidepressant and monoamine reuptake inhibitor activity) further demonstrated the efficacy and synthetic potential of this method. This journal is
- Huang, Fei,Huang, He,Hughes, Timothy,Xie, Yuxing,Xu, Jun,Yu, Yang,Zhang, Zhipeng
-
p. 4165 - 4173
(2020/07/14)
-
- N-monoarylacetothioureas as potent urease inhibitors: synthesis, SAR, and biological evaluation
-
A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16 ± 0.05 and 3.86 ± 0.10 μM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (koff=1.60 × 10?3 s?1) from the catalytic domain.
- Fang, Hai-Lian,He, Jie-Ling,Li, Wei-Yi,Liu, Shan-Shan,Ni, Wei-Wei,Pan, Xing-Ming,Xiao, Zhu-Ping,Ye, Ya-Xi,Yi, Juan,Zhou, Mi,Zhou, Tian-Li,Zhu, Hai-Liang
-
p. 404 - 413
(2020/01/03)
-
- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
-
A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
-
supporting information
p. 5242 - 5247
(2020/02/28)
-
- Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation
-
AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.
- Tng, Jiahui,Lim, Junxian,Wu, Kai-Chen,Lucke, Andrew J.,Xu, Weijun,Reid, Robert C.,Fairlie, David P.
-
supporting information
p. 5956 - 5971
(2020/06/05)
-
- One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles
-
We have identified a novel one-pot method for the synthesis of β-amino alcohols, which is based on C-H bond hydroxylation at the benzylic α-carbon atom with a subsequent nitrile or amide functional group reduction. This cascade process uses molecular oxygen as an oxidant and sodium bis(2-methoxyethoxy)aluminum hydride as a reductant. The substrate scope was examined on 30 entries and, although the respective products were provided in moderate yields only, the above simple protocol may serve as a direct and powerful entry to the sterically congested 1,2-amino alcohols that are difficult to prepare by other routes. The plausible mechanistic rationale for the observed results is given and the reaction was applied to a synthesis of a potentially bioactive target. This journal is
- Bobal, Pavel,Otevrel, Jan,Svestka, David
-
p. 25029 - 25045
(2020/07/14)
-
- Catalytic Direct α-Amination of Arylacetic Acid Synthons with Anilines
-
A unique α-amination approach using various anilines has been developed for arylacetic acids via adaptation as benzazoles. The reaction proceeds through a single electron transfer mechanism utilizing an iron-based catalyst system to access α-(N-arylamino)acetic acid equivalents. Modification of approved drugs, facile cleavage of the benzazole auxiliary, and tolerance of amide linkage forming conditions constitute the potential applicability of this strategy.
- Kumar, Jogendra,Suresh, Eringathodi,Bhadra, Sukalyan
-
p. 13363 - 13374
(2020/11/02)
-
- Coordination behaviors of diphenylketene adsorbed in the nanocages of zeolite NaY and AgY
-
We investigated in detail how polar cumulene molecules like diphenylketene were accommodated in faujasite zeolite pores based on 13C CP/MAS and DD/MAS NMR analyses as well as quantum chemical calculations after adsorbing the molecule into the zeolite NaY or AgY having “hard” sodium ions or “soft” silver ions. Since the diphenylketene has such a specific structure that a carbonyl group (a hard base) is accumulated by a carbon-carbon double bond (a soft π base), which is conjugated with two benzene rings (soft π bases), it is possible for the diphenylketene to adopt multicoordination modes to different metal ions in the zeolite. Compared with the coordination modes of benzophenone and 1,1-diphenylethene adsorbed in the NaY and AgY, those of diphenylketene were identified, and specific coordination behaviors in the zeolite’s supercages were classified depending on the hard or soft metal characters: The C=O and phenyl coordination modes to Na+ in NaY prevail, while the C=C and phenyl coordination to Ag+ in AgY is favored. We also unveiled the difference in the molecular mobility depending on the types of cations in the zeolite by comparing the 13C CP/MAS and DD/MAS NMR spectra.
- Shibata, Shintaro,Masui, Yoichi,Onaka, Makoto
-
supporting information
p. 663 - 670
(2020/12/29)
-
- Electrochemical [4+2] Annulation-Rearrangement-Aromatization of Styrenes: Synthesis of Naphthalene Derivatives
-
We report the first electrochemical strategy to synthesize functionalized naphthalene derivatives through [4+2] annulation—rearrangement–aromatization from styrenes under mild conditions. The electrolysis does not require metals, oxidants and high valence substrates, indicating the atom and step-economy ideals. The dehydrodimer produced through [4+2] cycloaddition of 4-methoxy α-methyl styrene is isolated and proved to be the key intermediate for the following oxydehydrogenation to form carbon cation, which undergoes rearrangement–aromatization to afford the final products. This reaction represents a powerful access to construct multi-substituted naphthalene blocks in a single step.
- Ma, Yueyue,Lv, Jufeng,Liu, Chengyu,Yao, Xiantong,Yan, Guoming,Yu, Wei,Ye, Jinxing
-
supporting information
p. 6756 - 6760
(2019/04/17)
-
- Decarbonylation of phenylacetic acids by high valent transition metal halides
-
Triphenylacetic acid underwent unusual decarbonylation when allowed to react with a series of halides of group 4-6 metals in their highest oxidation state, in dichloromethane at ambient temperature. Thus, the reaction of CPh3COOH with MoCl5, in 1:1 molar ratio, afforded the trityl salt [CPh3][MoOCl4], 1, in 79% yield, while the 1:2 reaction of CPh3COOH with NbF5 afforded [CPh3][NbF6], 2, in 70% yield, NbOF3 being the metal co-product. CPh3COOH reacted with NbCl5, TiF4 and WOCl4 to give mixtures of compounds, however the cation [CPh3]+ was NMR identified in each case. [CPh3][NbCl6], 3, was isolated from NbCl5 and CPh3COCl, prior to being generated from CPh3COOH and PCl5. The reaction of CPh3COOH with TiCl4 was non-selective, and the salt [CPh3][Ti2Cl8(μ-κ2-O2CCPh3)], 4, was obtained in 18% yield. The decarbonylation reactions of CMePh2COCl and CMe2PhCOCl by means of NbCl5 led to the indanes 5a-b, which were isolated in 79-97% yields after hydrolysis of the mixtures and subsequent alumina filtration of the organic phases. The reactions of CH(Ph)2COOH with NbCl5 and WCl6 afforded NbCl4(OOCCHPh2), 6, and CHPh2COCl, respectively, as the prevalent species. CPh2(CH2CH2Br)COOH did not undergo CO release when allowed to interact with WCl6, instead selective intramolecular condensation to C(Ph)2C(O)OCH2CH2, 7, occurred. MeCCCOOH underwent hydrochlorination by WCl6 to give MeC(Cl)CHCOOH, 8, in 72% yield. All the products were fully characterized by elemental analysis, IR and multinuclear NMR spectroscopy. In addition, the solid state structures of 1, 2, 4, 7, and 8 were elucidated by X-ray diffraction.
- Bartalucci, Niccolò,Marchetti, Fabio,Zacchini, Stefano,Pampaloni, Guido
-
p. 5725 - 5734
(2019/05/10)
-
- Chemospecific Cyclizations of α-Carbonyl Sulfoxonium Ylides on Aryls and Heteroaryls
-
The functionalization of aryl and heteroaryls using α-carbonyl sulfoxonium ylides without the help of a directing group has remained so far a neglected area, despite the advantageous safety profile of sulfoxonium ylides. Described herein are the cyclizations of α-carbonyl sulfoxonium ylides onto benzenes, benzofurans and N-p-toluenesulfonyl indoles in the presence of a base in HFIP, whereas pyrroles and N-methyl indoles undergo cyclization in the presence of an iridium catalyst. Significantly, these two sets of conditions are chemospecific for each groups of substrates.
- Clare, Daniel,Dobson, Benjamin C.,Inglesby, Phillip A.,A?ssa, Christophe
-
supporting information
p. 16198 - 16202
(2019/11/03)
-
- Synthesis of novel proxyphylline derivatives with dual Anti-Candida albicans and anticancer activity
-
Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R ≥ 3 at conc. of 31, 36 and 20 μM, respectively) however not against normal mammalian Vero cell line in vitro (IC50 ≥ 280 μM) and Galleria mellonella in vivo. These compounds also displayed moderate antineoplastic activity against human breast adenocarcinoma (MCF-7) cell line (EC50 = 80 μM) and high against peripheral blood T lymphoblast (CCRF-CEM) (EC50 = 6.3–6.5 μM). In addition, 6 and 42 exerted: (1) dual activity against fungal adhesion and damage mature biofilm; (2) necrosis of planktonic cells due to loss of membrane function and of structural integrity; (3) biochemical (inhibition of sessile cell respiration) and morphological changes in cell wall polysaccharide contents. Therefore, leading proxyphylline derivatives can be employed to prevent cancer-associated biofilm Candida infections.
- Borowiecki, Pawe?,Wińska, Patrycja,Bretner, Maria,Gizińska, Ma?gorzata,Koronkiewicz, Miros?awa,Staniszewska, Monika
-
p. 307 - 333
(2018/03/21)
-
- Synthesis of phthalic acid derivatives: Via Pd-catalyzed alkoxycarbonylation of aromatic C-H bonds with alkyl chloroformates
-
A Pd(ii)-catalyzed alkoxycarbonylation of aromatic C-H bonds with alkyl chloroformates has been developed. A broad range of benzamides and alkyl chloroformates are compatible with this protocol. The reaction is operationally simple and scalable. The direct group could be readily removed to access substituted phthalic acid esters (PAEs), 1,2-dibenzyl alcohols and phthalamides. Besides alkoxycarbonylation of benzamide β-C-H bonds, γ-alkoxycarbonylation of 2-phenylacetamide is also feasible.
- Liao, Gang,Chen, Hao-Ming,Shi, Bing-Feng
-
supporting information
p. 10859 - 10862
(2018/10/02)
-
- The Conversion of tert-Butyl Esters to Acid Chlorides Using Thionyl Chloride
-
The reaction of tert-butyl esters with SOCl2 at room temperature provides acid chlorides in unpurified yields of 89% or greater. Benzyl, methyl, ethyl, and isopropyl esters are essentially unreactive under these conditions, allowing for the selective conversion of tert-butyl esters to acid chlorides in the presence of other esters.
- Greenberg, Jacob A.,Sammakia, Tarek
-
p. 3245 - 3251
(2017/03/23)
-
- Design, synthesis and in vitro activity of 1,4-disubstituted piperazines and piperidines as triple reuptake inhibitors
-
Monoamine transporters regulate the concentration of monoamine neurotransmitters, which are essential for vital physiological processes, and their dysfunction can cause several central nervous system diseases. Monoamine transporters currently appear to be the potential target in the management of these disorders. In this study, homologation and bioisosterism techniques have been used in the designing of new 1,4-disubstituted piperazines and piperidines. These derivatives were synthesized and evaluated as potential triple reuptake inhibitors for studying the structure-activity relationships. The most advanced compound, 1-(4-(5-benzhydryl-1H-tetrazol-1-yl)butyl)-4-(3-phenylpropyl)piperazine (2i), was able to inhibit monoamine neurotransmitter reuptake in an in vitro test (IC50?=?158.7?nM for 5-HT, 99?nM for NE and 97.5?nM for DA). These novel potent triple reuptake inhibitor-based 1,4-disubstituted piperazine and piperidine scaffolds deserve further systematic optimization and pharmacological evaluation.
- Paudel, Suresh,Acharya, Srijan,Yoon, Goo,Kim, Kyeong-Man,Cheon, Seung Hoon
-
p. 2266 - 2276
(2017/03/23)
-
- Iodobenzene Dichloride in the Esterification and Amidation of Carboxylic Acids: In-Situ Synthesis of Ph3PCl2
-
A novel, in-situ synthesis of dichlorotriphenylphosphorane (Ph3PCl2) is accomplished upon combining PPh3and the easily prepared hypervalent iodine reagent iodobenzene dichloride (PhICl2). The phosphorane is selectively generated in the presence of carboxylic acid or alcohol residues to rapidly produce acyl chlorides and alkyl chlorides in high yields. Addition of EtOH, PhOH, BnOH, Et2NH or CH2N2results in the direct synthesis of esters, amides and diazo ketones from carboxylic acids.
- Carle, Myriam S.,Shimokura, Grace K.,Murphy, Graham K.
-
supporting information
p. 3930 - 3933
(2016/08/24)
-
- New orally active diphenylmethyl-based ester analogues of dihydroartemisinin: Synthesis and antimalarial assessment against multidrug-resistant Plasmodium yoelii nigeriensis in mice
-
A new series of ester analogues of artemisinin 8a–f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g–j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis in Swiss mice via oral route. These diphenylmethyl-based ester analogues 8a–f were found to be 2–4 folds more active than the antimalarial drugs β-arteether 4 and artesunic acid 5. Ester 8a, the most active compound of the series, provided complete protection to the infected mice at 24?mg/kg?×?4?days as well as 12?mg/kg?×?4?days, respectively. In this model β-arteether provided 100% and 20% protection at 48?mg/kg?×?4?days and 24?mg/kg?×?4?days, respectively.
- Chaudhary, Sandeep,Naikade, Niraj K.,Tiwari, Mohit K.,Yadav, Lalit,Shyamlal, Bharti Rajesh K.,Puri, Sunil K.
-
p. 1536 - 1541
(2016/07/27)
-
- Method for preparation of 2-hydroxy-2,2-diphenyl-1-(p-methylphenyl)ethanone
-
The invention relates to a method for preparation of 2-hydroxy-2,2-diphenyl-1-(p-methylphenyl)ethanone, wherein the method includes the steps: a), carrying out a reaction of 2,2-diphenyl acetic acid with phosphorus trichloride to prepare 2,2-diphenyl acetyl chloride; b), carrying out a reaction of 2,2-diphenyl acetyl chloride with toluene to prepare 2,2-diphenyl-1-(p-methylphenyl)ethanone; c), carrying out a reaction of 2,2-diphenyl-1-(p-methylphenyl)ethanone with bromine to prepare 2-bromo-2,2-diphenyl-1-(p-methylphenyl)ethanone; and d), carrying out a reaction of 2-bromo-2,2-diphenyl-1-(p-methylphenyl)ethanone with an alkali liquid to prepare 2-hydroxy-2,2-diphenyl-1-(p-methylphenyl)ethanone. The method has simple synthesis process, greatly reduces the dangerousness of the reactions, reduces the pollution to the environment, and is favorable for amplified and industrialized production.
- -
-
Paragraph 0030; 0031
(2017/03/28)
-
- SUBSTITUTED BENZOTHIAZOLES AND THERAPEUTIC USES THEREOF FOR THE TREATMENT OF HUMAN DISEASES
-
The invention relates to a family of differently substituted benzothiazoles having an inhibitory activity against the enzyme casein kinase 1 (CK1), as a result of which they are suitable for use in the treatment or prevention of diseases caused by this enzyme, particularly diseases associated with circadian rhythm and inflammatory, autoimmune, psychiatric, neurodegenerative, neurological or ophthalmological diseases, as well as for inducing cell regeneration.
- -
-
Paragraph 0087
(2015/12/18)
-
- Hydroalumination of Ketenimines and Subsequent Reactions with Heterocumulenes: Synthesis of Unsaturated Amide Derivatives and 1,3-Diimines
-
The series of differently substituted ketenimines 1 was hydroluminated using di-iso-butyl aluminum hydride. For the sterically congested ketenimine 1a, preferred hydroalumination of the C=N-bond was proven by X-ray crystallography (compound 5a). In situ treatment of the hydroaluminated ketenimines 5 with various heterocumulenes like carbodiimides, isocycanates, isothiocyanates and ketenimines as electrophiles and subsequent hydrolytic workup resulted in novel enamine derived amide species in case of N-attack (sterically less hindered ketenimines) under formation of a new C-N-bond or in 1,3-diimines by C-C-bond-formation in case of bulky substituents at the ketenimine-nitrogen atom. Furthermore, domino reactions with more than 1 equiv of the electrophile or by subsequent addition of two different electrophiles are possible and lead to polyfunctional amide derivatives of the biuret type which are otherwise not easily accessible.
- Jin, Xing,Willeke, Matthias,Lucchesi, Ralph,Daniliuc, Constantin-Gabriel,Fr?hlich, Roland,Wibbeling, Birgit,Uhl, Werner,Würthwein, Ernst-Ulrich
-
p. 6062 - 6075
(2015/06/30)
-
- Preparation of 1,2,5-Trisubstituted 1H-Imidazoles from Ketenimines and Propargylic Amines by Silver-Catalyzed or Iodine-Promoted Electrophilic Cyclization Reaction of Alkynes
-
From readily available propargylic amines, 1,2,5-trisubstituted imidazoles are efficiently obtained through a cascade reaction catalyzed by AgOTf or promoted by molecular iodine. The AgOTf-catalyzed reaction involves nucleophilic addition of propargylic amine to ketenimine, a silver-catalyzed electrophilic cyclization reaction of alkyne, and a tautomerism/isomerism/metal-H exchange cascade. The iodine-mediated counterpart yields 5-formyl-1,2-disubtituted imidazoles, which presumably includes a cascade hydrolysis/oxidation reaction. Furthermore, the presented protocol can be scaled up and the resultant 1,2,5-trisubstituted imidazole can be converted into fused indeno[1,2-d]imidazole. 1,2,5-Trisubstituted imidazoles are efficiently prepared from readily available propargylic amines through a AgOTf-catalyzed or molecular iodine-promoted cascade reaction. The presented protocol can be scaled up and the resultant 1,2,5-trisubstituted imidazoles can be converted into fused indeno[1,2-d]imidazoles.
- Zhou, Xiaorong,Jiang, Zheng,Xue, Lexing,Lu, Ping,Wang, Yanguang
-
supporting information
p. 5789 - 5797
(2015/09/15)
-
- Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors
-
A series of 4-benzylpiperidine carboxamides were designed and synthesized, and tested for their dual (serotonin and norepinephrine) reuptake inhibition. The synthesis of 4-benzylpiperidine carboxamides involved two main steps: amidation and substitution. Derivatives with 3 carbon linker displayed better activity than with 2 carbon linker. 4-Biphenyl- and 2-naphthyl-substituted derivatives 7e and 7j showed greater dual reuptake inhibition than standard drug venlafaxine HCl.
- Paudel, Suresh,Cao, Yongkai,Guo, Shuohan,An, Byeongkwan,Kim, Kyeong-Man,Cheon, Seung Hoon
-
p. 6418 - 6426
(2015/10/05)
-
- Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis
-
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons in cortex, brain stem, and spinal cord die progressively, resulting in muscle wasting, paralysis, and death. Currently, effective therapies for ALS are lacking; however, identification of pathological TAR DNA-binding protein 43 (TDP-43) as the hallmark lesion in sporadic ALS suggests new therapeutic targets for pharmacological intervention. Pathological TDP-43 phosphorylation appears to drive the onset and progression of ALS and may result from upregulation of the protein kinase CK-1 in affected neurons, resulting in postranslational TDP-43 modification. Consequently, brain penetrant specific CK-1 inhibitors may provide a new therapeutic strategy for treating ALS and other TDP-43 proteinopathies. Using a chemical genetic approach, we report the discovery and further optimization of a number of potent CK-1δ inhibitors. Moreover, these small heterocyclic molecules are able to prevent TDP-43 phosphorylation in cell cultures, to increase Drosophila lifespan by reduction of TDP-43 neurotoxicity, and are predicted to cross the blood-brain barrier. Thus, N-(benzothiazolyl)-2-phenyl-acetamides are valuable drug candidates for further studies and may be a new therapeutic approach for ALS and others pathologies in which TDP-43 is involved.
- Salado, Irene G.,Redondo, Miriam,Bello, Murilo L.,Perez, Concepción,Liachko, Nicole F.,Kraemer, Brian C.,Miguel, Laetitia,Lecourtois, Magalie,Gil, Carmen,Martinez, Ana,Perez, Daniel I.
-
p. 2755 - 2772
(2014/04/17)
-
- Prodrugs of N-dicarboximide derivatives of the rat selective toxicant norbormide
-
Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2- pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, one major drawback of NRB as a viable rodenticide relates to an evolutionary aversion developed by the rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid onset of effects. A series of NRB-derived prodrugs were prepared in an effort to 'mask' this acute response. Their synthesis and biological evaluation (in vitro vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and lethality/palatability in vivo) is described. Prodrug 2 displayed the most promising profile with respect to a delay in the onset of symptoms and was subsequently demonstrated to be significantly more palatable to rats. Moreover, prodrug 25 was found to be largely accepted by rats in a choice trial, resulting in high mortality.
- Rennison, David,Laita, Olivia,Conole, Daniel,Jay-Smith, Morgan,Knauf, Jan,Bova, Sergio,Cavalli, Maurizio,Hopkins, Brian,Linthicum, Darwin S.,Brimble, Margaret A.
-
p. 5886 - 5899
(2013/09/12)
-
- THIENO [2,3-B] PYRIDINEDIONE ACTIVATORS OF AMPK AND THERAPEUTIC USES THEREOF
-
The invention relates to compounds that are direct activators of AMPK (AMP- activated protein kinase) and their use in the treatment of disorders regulated by activation of AMPK. For instance, compounds according to the invention are useful for the treatment of diabetes, metabolic syndrome, obesity, inflammation, cancer and cardiovascular diseases.
- -
-
Page/Page column 58-59
(2011/07/30)
-
- A dinuclear palladium catalyst for α-Hydroxylation of carbonyls with O2
-
A chemo- and regioselective α-hydroxylation reaction of carbonyl compounds with molecular oxygen as oxidant is reported. The hydroxylation reaction is catalyzed by a dinuclear Pd(II) complex, which functions as an oxygen transfer catalyst, reminiscent of an oxygenase. The development of this oxidation reaction was inspired by discovery and mechanism evaluation of previously unknown Pd(III)-Pd(III) complexes.
- Chuang, Gary Jing,Wang, Weike,Lee, Eunsung,Ritter, Tobias
-
supporting information; experimental part
p. 1760 - 1762
(2011/04/15)
-
- Reducing the cost, smell, and toxicity of the Barton reductive decarboxylation: Chloroform as the hydrogen atom source
-
When used as solvent, chloroform was found to act as a hydrogen atom donor in Barton reductive decarboxylation reactions. Chloroform offers a substantial practical advantage over pre-existing hydrogen atom donors.
- Ko, Eun Jung,Williams, Craig M.,Savage, G. Paul,Tsanaktsidis, John
-
supporting information
p. 1944 - 1947
(2015/02/18)
-
- A mild titanium-based system for the reduction of amides to aldehydes
-
A mild method for the reduction of amides to aldehydes using 1,1,3,3-tetramethyldisiloxane/titanium(IV) isopropoxide reducing system is described. The reaction occurs under mild conditions and allows the reduction of aromatic as well as aliphatic, tertiary amides to the corresponding aldehydes, in good yields. This methodology was extended to the reduction of aromatic secondary and primary amides to the corresponding aldehydes.
- Laval, Stéphane,Dayoub, Wissam,Favre-Reguillon, Alain,Demonchaux, Patrice,Mignani, Gérard,Lemaire, Marc
-
body text
p. 2092 - 2094
(2010/06/14)
-
- Structure-activity relationships studies in a series of N,N-bis(alkanol)amine aryl esters as P-glycoprotein (Pgp) dependent multidrug resistance (MDR) inhibitors
-
As a continuation of a previous research, a series of N,N-bis(alkanol)amine aryl esters, as Pgpdependent MDR inhibitors, was designed and synthesized. The aromatic ester portions are suitably modulated, and new aryl rings (Ar 1 and Ar2) were combined with trans-3-(3,4,5- trimethoxyphenyl)vinyl, 3,4,5-trimethoxybenzyl and anthracene moieties that were present in the most potent previously studied compounds. The new compounds showed a wide range of potencies and efficacies on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Selected compounds (5, 6, 8, 9, and 21) were further studied, evaluating their action on doxorubicin cytotoxicity potentiation on K562 cells; they significantly enhanced doxorubicin cytotoxicity on K562/DOX cells, confirming the results obtained with pirarubicin. Compound, 9 shows the most promising properties as it was able to nearly completely reverse Pgp-dependent pirarubicin extrusion at nanomolar doses and increased the cytotoxicity of doxorubicin with a reversal fold (RF) of 19.1. at 3 μM dose.
- Martelli, Cecilia,Coronnello, Marcella,Dei, Silvia,Manetti, Dina,Orlandi, Francesca,Scapecchi, Serena,Romanelli, Maria Novella,Salerno, Milena,Mini, Enrico,Teodori, Elisabetta
-
scheme or table
p. 1755 - 1762
(2010/08/06)
-
- Advances towards highly active and stereoselective simple and cheap proline-based organocatalysts
-
Ten 4-acyloxy-L-prolines were screened as catalysts at loadings of 2-0.1 mol-% for the direct asymmetric aldol reaction in water by using variable amounts of water. Among them, a new catalyst, the L-proline carrying a trans-4-(2,2-diphenylacetoxy) group, and a catalyst previously synthesized by us, the L-proline carrying a trans-4-(4-phenylbutanoyloxy) group, were found to be excellent catalysts for the aldol reaction between cyclohexanone or cyclopentanone and substituted benzaldehydes when employed in only 1 and 0.5 mol-%,respectively, at room temperature without additives. For such catalysts, high turnover numbers were obtained, which are among the highest values obtained for enamine organocatalysis. Finally, these catalysts can be synthesized by direct O-acylation from inexpensive molecules and successfully used in scaled-up reactions. Highest activity and selectivity at minor expense! Simple and cheap 4-acyloxy-L-prolines were easily prepared and successfully employed in the direct asymmetric aldol reaction in water by using a loading of2-0.1 mol-%. Interestingly, high turnover numbers, among the highest values ever reported for enamine organocatalysis, were obtained.
- Giacalone, Francesco,Gruttadauria, Michelangelo,Agrigento, Paola,Lo Meo, Paolo,Noto, Renato
-
experimental part
p. 5696 - 5704
(2010/12/25)
-
- A convenient, one-pot procedure for the preparation of acyl and sulfonyl fluorides using Cl3CCN, Ph3P, and TBAF(t -BuOH) 4
-
Various carboxylic acids were converted into acyl fluorides in excellent yields by treatment with trichloroacetonitrile, triphenylphosphine, and TBAF(t-BuOH)4 at room temperature. The reaction was applicable to the preparation of acid-sensitive amino acid fluorides without deprotection or rearrangement
- Kim, Joong-Gon,Jang, Doo Ok
-
experimental part
p. 3049 - 3052
(2011/02/25)
-
- An investigation into the electrophilic cyclisation of N-acyl-pyrrolidinium ions: A facile synthesis of Pyrrolo-tetrahydroisoquinolones and Pyrrolo-benzazepinones
-
The triflic acid-mediated cyclisation of N-arylmethyl- and N-arylethyl-acylpyrrolidinium ions gave moderate to good yields of pyrrolo-tetrahydroisoquinolones and pyrrolo-benzazepinones respectively. Electron-donating R substituents enhanced the rate of reaction and gave higher yields than electron-withdrawing substituents. Substituents on the methyl or ethyl chain in general enhanced the reaction, unless sterically encumbered. The equivalent acylpiperidinium ions cyclised much slower and in lower yield.
- King, Frank D.,Aliev, Abil E.,Caddick, Stephen,Copley, Royston C. B.
-
experimental part
p. 3561 - 3571
(2010/01/06)
-
- Synthesis and pharmacological screening of several aroyl and heteroaroyl selenylacetic acid derivatives as cytotoxic and antiproliferative agents
-
The synthesis and cytotoxic activity of a series of twenty six aroyl and heteroaroyl selenylacetic acid derivatives of general formula Ar-CO-Se-CH2-COOH or Heterar-CO-Se-CH2-COOH are reported. The synthesis was carried out by reaction of acyl chlorides with sodium hydrogen selenide, prepared in situ, and this led to the formation of sodium aroylselenides that subsequently reacted with --bromoacetic acid to produce the corresponding selenylacetic acid derivatives. All of the compounds were tested against a prostate cancer cell line (PC-3) and some of the more active compounds were assessed against a panel of four human cancer cell lines (CCRF-CEM, HTB-54, HT-29, MCF-7) and one mammary gland-derived non-malignant cell line (184B5). Some of the compounds exhibited remarkable cytotoxic and antiproliferative activities against MCF-7 and PC-3 that were higher than those of the reference compounds doxorubicin and etoposide, respectively. For example, in MCF-7 when Ar=phenyl, 3,5-dimethoxyphenyl or benzyl the TGI values were 3.69, 4.18 and 6.19 -M. On the other hand, in PC-3 these compounds showed values of 6.8, 4.0 and 2.9 -M. Furthermore, benzoylselenylacetic acid did not provoke apoptosis nor did it perturb the cell cycle in MCF-7.
- Sanmartin, Carmen,Plano, Daniel,Dominguez, Enrique,Font, Maria,Calvo, Alfonso,Prior, Celia,Encio, Ignacio,Palop, Juan Antonio
-
scheme or table
p. 3313 - 3338
(2010/03/04)
-
- Efficient synthesis and biological evaluation of two modafinil analogues
-
Non classical bioisosters of modafinil featuring interesting biological profile have been easily produced through replacement of the sulfoxide function with a carbonyl group and modification of the carboxylic acid amide functionality.
- De Risi, Carmela,Ferraro, Luca,Pollini, Gian P.,Tanganelli, Sergio,Valente, Filippo,Veronese, Augusto C.
-
experimental part
p. 9904 - 9910
(2009/04/06)
-
- Reactivity of chlorinating agents/PPh3 for the chlorination of alcohols and carboxylic acids: a comparative study
-
The reactivity of chlorinating agents was examined with the aid of 1H NMR using competitive reactions between selected chlorinating agents and CBr4 towards alcohols and carboxylic acids. The reactivity was greatly dependent on the type of substituent on the chlorinating agents. COCCl3 and CN substituted trichloromethyl groups enhanced the reactivity of the chlorinating agent with PPh3 for the chlorination of alcohols and carboxylic acids.
- Pluempanupat, Wanchai,Chantarasriwong, Oraphin,Taboonpong, Piyada,Jang, Doo Ok,Chavasiri, Warinthorn
-
p. 223 - 226
(2007/10/03)
-
- Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors
-
In this report, we describe new HDAC inhibitors designed to exploit a unique sub-pocket in the HDAC8 active site. These compounds were based on inspection of the available HDAC8 crystal structures bound to various inhibitors, which collectively show that the HDAC8 active site is unusually malleable and can accommodate inhibitor structures that are distinct from the canonical 'zinc binding group-linker-cap group' structures of SAHA, TSA, and similar HDAC inhibitors. Some inhibitors based on this new scaffold are >100-fold selective for HDAC8 over other class I and class II HDACs with IC50 values 1 μM against HDAC8. Furthermore, treatment of human cells with the inhibitors described here shows a unique pattern of hyperacetylated proteins compared with the broad-spectrum HDAC inhibitor TSA.
- KrennHrubec, Keris,Marshall, Brett L.,Hedglin, Mark,Verdin, Eric,Ulrich, Scott M.
-
p. 2874 - 2878
(2008/02/03)
-
- Synthesis and biological evaluation of benzimidazole derivatives as potent AMP-activated protein kinase activators
-
Design, synthesis and structure-activity relationships of benzimidazole derivatives as activators of the AMP-activated protein kinase (AMPK) are presented in this paper. AMPK is the central component of a protein kinase cascade that plays a key role in the regulation of energy balance. Once activated, AMPK initiates a series of responses that are aimed at restoring the energy balance of the cell and recent studies have indicated that AMPK plays an important role in regulation of the whole-body energy metabolism. The following study based on the lead compound S27847 involved modification of three regions of this compound. Preliminary structure-activity relationships are being described.
- Charton, Julie,Girault-Mizzi, Sophie,Debreu-Fontaine, Marie-Ange,Foufelle, Fabienne,Hainault, Isabelle,Bizot-Espiard, Jean-Guy,Caignard, Daniel-Henri,Sergheraert, Christian
-
p. 4490 - 4518
(2007/10/03)
-
- SYNTHESIS OF STERICALLY HINDERED SECONDARY AMINOETHER ALCOHOLS
-
Severely sterically hindered secondary aminoether alcohols are prepared by reacting organic carboxylic, organic carboxylic acid halides, acid anhydrides or a ketene with an alkyl, alkaryl or alkylhalo sulfonate to yield a sulfonic. Carboxylic anhydride compound which is then reacted with a dioxane to cleave the ring of the dioxane, yielding a cleavage product which cleavage product is then aminated with an alkylamine and hydrolyzed with base to yield the severely sterically hindered secondary aminoether alcohol.
- -
-
Page/Page column 22
(2008/06/13)
-
- Conversion of sterically hindered diacylated 1,2-phenylenediamines into 2-substituted benzimidazoles
-
A series of bulky 2-substituted benzimidazoles was designed in order to find new leads for several biological targets. Formation by cyclodehydration from their monoacylated counterparts was shown to be strongly dependent upon the nature of the acyl group. In the case of a dicyclohexylmethyl group, cycllzation was only observed in a p-toluenesulfonic acid/toluene mixture from the symmetrical diacylated precursor. Analysis of the mechanism was begun starting from mixed diacylated derivatives.
- Charton, Julie,Girault-Mizzi, Sophie,Sergheraert, Christian
-
p. 492 - 497
(2007/10/03)
-
- Synthesis and identification of small molecules that potently induce apoptosis in melanoma cells through G1 cell cycle arrest
-
Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenylmethylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC50 ~ 0.5 μM), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor κ-B (NFκB) in the cell; NFκB is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NFκB and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.
- Dothager, Robin S.,Putt, Karson S.,Allen, Brittany J.,Leslie, Benjamin J.,Nesterenko, Vitaliy,Hergenrother, Paul J.
-
p. 8686 - 8696
(2007/10/03)
-
- Synthesis and antitumour activity of new derivatives of flavone-8-acetic acid (FAA). Part 4: Variation of the basic structure
-
A range of 11 derivatives of flavone-8-acetic acid (FAA) in which the structure has been substantially altered in different ways have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. The generally poor activity observed shows that the basic structure cannot be altered much without destroying the activity.
- Alan Aitken,Bibby, Michael C.,Cooper, Patricia A.,Double, John A.,Laws, Andrea L.,Ritchie, Robert B.,Wilson, David W.J.
-
p. 181 - 188
(2007/10/03)
-
- Asymmetric catalysis, 131([≠]) - Naproxen derivatives by enantioselective decarboxylation
-
A new catalytic method to synthesize the important anti-inflammatory agent naproxen [(S)-1] which has to be used as the (S) enantiomer, involves the enantioselective decarboxylation of the 6-methoxynaphth-2-yl derivative 2 of 2-cyanopropionic acid. Compound 2 was stirred in THF at 15 °C with catalytic amounts of chiral bases, which abstracted the carboxyl proton. After decarboxylation, reprotonation of the anion of 6 afforded the enantiomerically enriched naproxen nitrile 6, which may be hydrolyzed to naproxen. A variety of bases were screened, and cinchona alkaloids were found to give the best enantioselectivities. Thus, with quinidine 10, up to 34% ee was obtained for (S)-6. The enantiomeric excess could be increased by turning to amides of 9-amino-9-deoxyepicinchona alkaloids. The most successful 2- ethoxybenzantide 31a of 9-amino-9-deoxyepicinchonine 11 gave up to 71.9% ee (S)-6. Cyclic ethers like THF were suitable solvents, and at a temperature of 15 °C, conversion was quantitative within 24 h in most cases. For high enantioselectivities, 5-10 mol-% of chiral base was sufficient, and the catalyst could be fully recycled after decarboxylation. The model compound 2- cyano-2-phenylpropionic acid (40) was decarboxylated with base 31a to the (S) enantiomer of the corresponding nitrile 41 with 60% ee.
- Brunner, Henri,Schmidt, Peter
-
p. 2119 - 2133
(2007/10/03)
-
- New orally active enkephalinase inhibitors: Their synthesis, biological activity, and analgesic properties
-
A series of (4s)-4-[(2S)-benzyl-3-mercaptopropionylamino]-4-(N- phenylcarbamoyl)-butyric acids has been identified as potent systemically active enkephalinase inhibitors. Structure-activity relationships (SAR) are discussed. Further chemical modification of the inhibitors was carried out in order to identify the inhibitors which are orally active in an animal model. Compounds of particular interest are the prodrug-like analogues, including 5b (ONO-9902). Their analgesic effects after oral administration were evaluated.
- Senokuchi, Kazuhiko,Nakai, Hisao,Nagao, Yuuki,Sakai, Yasuhiro,Katsube, Nobuo,Kawamura, Masanori
-
p. 441 - 463
(2007/10/03)
-
- Synthesis, antimuscarinic activity and quantitative structure-activity relationship (QSAR) of tropinyl and piperidinyl esters
-
A series of tropinyl and piperidinyl esters was synthesized and evaluated for inhibitory activities on the endothelial muscarinic receptors of rat (M3) and rabbit (M2) aorta. Some of the esters (cyclohexylphenylglycolates and cyclohexylphenylpropionates) were found to be better antimuscarinic compounds than standard M2 and M3 inhibitors such as AFDX116 and 4-diphenylacetoxy-N-methylpiperidine (DAMP), with pKEC50 values in the range of 8-9. A few esters were found to be more selective M3 than M2 inhibitors, but these tended to have low activities. The hydrophobic, electronic and steric characteristics of these esters were correlated with antimuscarinic activity by using appropriate parameters representing hydrophobicity (HPLC capacity factor, log k(w), size (molecular volume) and electronic character (Taft's polar substituent constant δ and 13C chemical shift difference Δδ). Finally, 92% of the M2-inhibitory activities of the esters could be accounted for by the size and electronic character σ* of the side chain. In contrast, the M3-inhibitory activities of these esters were mainly attributed to the electronic nature (σ*, Δδ) of the side chain, with good activity being associated with electron-withdrawing groups. Visualization of the comparative molecular field analysis (CoMFA) steric and electrostatic fields provided further confirmation of the structure-activity relationship (SAR) derived from traditional quantitative structure-activity relationship (QSAR) approaches.
- Xu, Rong,Sim, Meng-Kwoon,Go, Mei-Lin
-
p. 231 - 241
(2007/10/03)
-
- Trans N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] cycloprop-2-ene-1-carboxamides: Novel lipophilic kappa opioid agonists
-
The synthesis and kappa opioid agonist activities of some lipophilic analogues of the kappa opioid agonist U-50488 incorporating motifs bearing two aromatic rings in place of the 3,4-dichlorophenyl group are described. Trans 2,3-diphenyl-N-methyl-N[2-(1-pyrrolidinyl)cyclohexyl]-2-cyclopropene-1 -carboxamide, 7, is a potent kappa opioid agonist. A diphenylcyclopropene analogue of CI-977, trans 2,3-diphenyl-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-2 -cyclopropene-1-carboxamide, 13, is a highly lipophilic chemically novel potent selective kappa opioid agonist.
- Sabin,Horwell,McKnight,Broqua
-
p. 291 - 296
(2007/10/03)
-