- Expedient Approach to 6-Bromo-2-isopropylidenecoumaranone, a Potential Intermediate for the Synthesis of TMC-120B, Pseudodeflectusin, and Their Congeners
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A straightforward approach toward 6-bromo-2-isopropylidenecoumaranone, a potential intermediate toward alkaloid TMC 120-B, pseudodeflectusin, and other natural products, was reported. The synthetic sequence involved the reaction of 3-bromosalicylaldehyde with chloroacetone and cyclization of the resulting ether to a 2-acetylcoumaranol intermediate. This was followed by sequential methyl Grignard addition and Jones' oxidation to the corresponding coumaranone, which was dehydrated to the final product with the methanesulfonyl chloride/pyridine reagent. The protection of the coumaranol as the corresponding THP-ether resulted in improved product yields.
- Pergomet, Jorgelina L.,Kaufman, Teodoro S.,Bracca, Andrea B. J.
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Read Online
- Divergent Synthesis of Dihydroxanthene-Hemicyanine Fused Near-Infrared Fluorophores through the Late-Stage Amination of a Bifunctional Precursor
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A late-stage amination of a bifunctional dihydroxanthene (DHX) scaffold is reported to access a wide variety of new near-infrared (NIR) chromophores/fluorophores. The divergent approach allows the coupling of aliphatic and aromatic amines and readily provides molecular diversity shedding light on the structure-fluorescence relationship of this emerging class of NIR fluorophores.
- Ong, Michelle Jui Hsien,Srinivasan, Rajavel,Romieu, Anthony,Richard, Jean-Alexandre
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Read Online
- Synthesis and physical properties of novel liquid crystals containing pyranobenzopyrans as a core structure
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The synthesis and physical properties of pyranobenzopyran ring system have been studied as a core structure of novel liquid crystal (LC) compounds. Substituted pyranobenzopyrans having an alkoxy group on the A ring (benzene ring) exhibited smectic and nematic phase, those having a fluoro-substituted phenyl group on the A ring exhibited wider range of smectic phase. When the latter are added to a base LC mixture (ZLI-1565, Merck), the clearing point was raised. Interestingly, pyranobenzopyrans having a trifluoromethyl phenyl group or a cyano group on the A ring showed an extremely large positive dielectric anisotropy. The Royal Society of Chemistry 2005.
- Inoue, Seiichi,Yanai, Takayoshi,Ando, Shinji,Nakazawa, Akinori,Honda, Kiyoshi,Hoshino, Yujiro,Asai, Tomoyuki
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Read Online
- Synthesis and spectral properties of 6′-triazolyl-dihydroxanthene-hemicyanine fused near-infrared dyes
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We describe the synthesis of a range of 6′-triazolyl-dihydroxanthene-hemicyanine (DHX-hemicyanine) fused dyes through an effective copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click"reaction, with the aim of providing molecular diversity and evaluating the spectral properties of these near-infrared (NIR)-active materials. This was implemented by reacting 15 different aliphatic and aromatic azides with a terminal alkynyl-based DHX-hemicyanine hybrid scaffold prepared in four steps and 35% overall yield from 4-bromosalicylaldehyde. The resulting triazole derivatives have been fully characterized and their optical properties determined both in organic solvents and under simulated physiological conditions (phosphate buffered saline containing 5% of bovine serum albumin protein). This systematic study is a first important step towards the development of NIR-I fluorogenic "click-on"dyes or related photoactive agents for light-based diagnostic and/or therapeutic applications.
- Gu, Lingyue,Renault, Kévin,Romieu, Anthony,Richard, Jean-Alexandre,Srinivasan, Rajavel
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supporting information
p. 12208 - 12215
(2020/07/30)
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- A Facile Synthesis of Ligands for the von Hippel-Lindau E3 Ligase
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The proteolysis-targeting chimeras (PROTACs) have become an integral part of different stages of drug discovery. This growing field, therefore, benefits from advancements in all segments of the design of these compounds. Herein, an efficient and optimized synthetic protocol to various von Hippel-Lindau (VHL) ligands is presented, which enables easy access to multigram quantities of these essential PROTAC building blocks. Moreover, the elaborated synthesis represents a straightforward approach to further explore the chemical space of VHL ligands.
- Bricelj, Ale?a,Gütschow, Michael,Schnakenburg, Gregor,Sosi?, Izidor,Steinebach, Christian,Voell, Sabine Anna,Vu, Lan Phuong
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supporting information
p. 2521 - 2527
(2020/09/07)
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- Phosphine-Catalyzed [3+2] Annulation of β-Sulfonamido-Substituted Enones with Sulfamate-Derived Cyclic Imines
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Phosphine-catalyzed [3+2] annulation of β-sulfonamido-substituted enones and sulfamate-derived cyclic imines has been developed, giving a series of imidazoline derivatives in moderate to excellent yields with good to excellent diastereoselectivities. A scale-up reaction worked well under mild reaction conditions. A possible mechanism was proposed on the basis of the results obtained.
- Shi, Wangyu,Zhou, Leijie,Mao, Biming,Wang, Qijun,Wang, Chang,Zhang, Cheng,Li, Xuefeng,Xiao, Yumei,Guo, Hongchao
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supporting information
p. 679 - 685
(2019/01/24)
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- Manufacture of the PI3K β-Sparing Inhibitor Taselisib. Part 1: Early-Stage Development Routes to the Bromobenzoxazepine Core
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Two convergent regioselective routes for the synthesis of the tetracyclic imidazobenzoxazepine triazole 1, a key intermediate toward the synthesis of taselisib, are described. In the first-generation route, a chemoselective Negishi cross-coupling reaction was developed between iodoimidazole 3 and triazole 7, which enabled the delivery of initial kilogram quantities of 1. Because of the inefficiencies in the preparation of the imidazole 3, a second-generation route via a highly regioselective imidazole ring formation between α-chloroketone 11 and aryl amidine 12 was developed. The resulting imidazole 14 provided the handle to efficiently install the seven-membered benzoxazepine ring system in one pot with two-step N-alkylation and SNAr tandem reactions.
- Remarchuk, Travis,Angelaud, Rémy,Askin, David,Kumar, Archana,Thompson, Andrew S.,Cheng, Hua,Reichwein, John F.,Chen, Yanping,St-Jean, Frédéric
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supporting information
p. 775 - 782
(2019/05/24)
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- Enantioselective Construction of Tetrahydroquinazoline Motifs via Palladium-Catalyzed [4 + 2] Cycloaddition of Vinyl Benzoxazinones with Sulfamate-Derived Cyclic Imines
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A palladium-catalyzed enantioselective [4 + 2] cycloaddition reaction of vinyl benzoxazinones with sulfamate-derived cyclic imines is described, affording the tetrahydroquinazolines bearing several functional rings in high yields (up to 99% yield) with good to excellent diastereoselectivities and excellent enantioselectivities (up to 96% ee). This reaction represents the first Pd-catalyzed asymmetric decarboxylative cycloaddition of vinyl benzoxazinones with imines.
- Wang, Chang,Li, Yan,Wu, Yang,Wang, Qijun,Shi, Wangyu,Yuan, Chunhao,Zhou, Leijie,Xiao, Yumei,Guo, Hongchao
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supporting information
p. 2880 - 2883
(2018/05/29)
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- BENZOXAZEPIN OXAZOLIDINONE COMPOUNDS AND METHODS OF USE
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Described herein are benzoxazepin oxazolidinone compounds with phosphoinositide- 3 kinase (PI3K) modulation activity or function having the Formula (I) structure: or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such PI3K modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon PI3K dysregulation.
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Page/Page column 69; 71
(2017/01/26)
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- BENZOXAZEPIN OXAZOLIDINONE COMPOUNDS AND METHODS OF USE
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Described herein are benzoxazepin oxazolidinone compounds with phosphoinositide-3 kinase (PI3K) modulation activity or function having the Formula I structure: or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such PI3K modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon PI3K dysregulation.
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Paragraph 0150; 0165-0166
(2017/01/23)
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- Metabolic epoxidation is a critical step for the development of benzbromarone-induced hepatotoxicity
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Benzbromarone (BBR) is effective in the treatment of gout; however, clinical findings have shown it can also cause fatal hepatic failure. Our early studies demonstrated that CYP3A catalyzed the biotransformation of BBR to epoxide intermediate(s) that reacted with sulfur nucleophiles of protein to form protein covalent binding both in vitro and in vivo. The present study attempted to define the correlation between metabolic epoxidation and hepatotoxicity of BBR by manipulating the structure of BBR. We rationally designed and synthesized three halogenated BBR derivatives, fluorinated BBR (6-F-BBR), chlorinated BBR (6-Cl-BBR), and brominated BBR (6-Br-BBR), to decrease the potential for cytochrome P450-mediated metabolic activation. Both in vitro and in vivo uricosuric activity assays showed that 6-F-BBR achieved favorable uricosuric effect, while 6-Cl-BBR and 6-Br-BBR showed weak uricosuric efficacy. Additionally, 6-F-BBR elicited much lower hepatotoxicity in mice. Fluorination of BBR offered advantage to metabolic stability in liver microsomes, almost completely blocked the formation of epoxide metabolite(s) and protein covalent binding, and attenuated hepatic and plasma glutathione depletion. Moreover, the structural manipulation did not alter the efficacy of BBR. This work provided solid evidence that the formation of the epoxide(s) is a key step in the development of BBR-induced hepatotoxicity.
- Wang, Wenbao,Wang, Shaojie,Zhang, Tingjian,Lan, Qunsheng,Pang, Jianxin,Wang, Hui,Peng, Ying,Zhao, Huimin,Zhao, Yufei,Wang, Xu,Zheng, Jiang
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supporting information
p. 1354 - 1363
(2019/01/12)
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- Phosphine-Catalyzed [4 + 2] Annulation of Allenoate with Sulfamate-Derived Cyclic Imines: A Reaction Mode Involving γ′-Carbon of α-Substituted Allenoate
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A phosphine-catalyzed [4 + 2] cycloaddition of cyclic α-substituted allenoates with sulfamate-derived cyclic imines has been reported. Using dibenzylphenylphosphine as the nucleophilic catalyst, the reaction worked efficiently to yield various fused multicyclic heterocyclic compounds in high yields with excellent diastereoselectivities. It undergoes a new reaction mode involving γ′-carbon of α-substituted allenoate.
- Mao, Biming,Shi, Wangyu,Liao, Jianning,Liu, Honglei,Zhang, Cheng,Guo, Hongchao
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supporting information
p. 6340 - 6343
(2017/12/08)
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- Synthesis method of 2-hydroxyl-4-bromobenzoic acid
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The present invention discloses a synthesis method of 2-hydroxyl-4-bromobenzoic acid, and belongs to the technical field of organic synthesis. According to the synthesis method disclosed by the present invention, the synthesis method comprises the following steps: using phenol as a raw martial; firstly adding nitric acid and sulfuric acid to generate 2-nitrophenol; then adding HCl and zinc powder to synthesize 2-amino phenol; heating in a water bath and adding CH3COCH to further generate 2-acetamidophenol; next, adding FeBr3 and Br2, and adding CaO2 and triiron tetroxide after the reaction is cooled; and thus generating the 2-hydroxyl-4-bromobenzoic acid disclosed by the present invention after the 2-acetamidophenol is changed into the 2-hydroxyl-4-bromobenzoic acid. The embodiment demonstrates that the synthesis method disclosed by the present invention is not only simple in operation and mild in reaction but also free of pollution, so that the product yield is higher than 89%, and the purity reaches more than 92%.
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- Radioactive iodine labeled compound, and, radioactive pharmaceutical containing the same (by machine translation)
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PROBLEM TO BE SOLVED: and compatibility and affinity for both amyloidosis acryloyldimethyltauric, labeled compd. radioactive iodine. SOLUTION: the present invention, N, N-labeled compd. dimethyl benzene amine including radioactive iodine or its salt. Selected drawing: no (by machine translation)
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Paragraph 0016; 0037; 0055; 0056
(2018/10/10)
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- Structure-Activity Relationship Study of Heterocyclic Phenylethenyl and Pyridinylethenyl Derivatives as Tau-Imaging Agents That Selectively Detect Neurofibrillary Tangles in Alzheimers Disease Brains
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In order to explore novel tau-imaging agents that can selectively detect neurofibrillary tangles in Alzheimers disease (AD) brains, we designed and synthesized a series of heterocyclic phenylethenyl and (3-pyridinyl)ethenyl derivatives with or without a dimethyl amino group. In in vitro autoradiography using AD brain sections, all radioiodinated ligands with a dimethyl amino group bound to Aβ deposits in the sections. In contrast, the ligands without a dimethyl amino group showed different patterns of radioactivity accumulation in the sections depending on the kind of heterocycle contained in their molecules. Particularly, a phenylethenyl benzimidazole derivative ([125I]64) showed marked radioactivity accumulation in the temporal lobe which corresponded with the distribution of tau deposits. [125I]64 also showed the most favorable pharmacokinetics in normal mouse brains (3.69 and 0.06% ID/g at 2 and 60 min postinjection, respectively) among all ligands in this study. Taken together, these results suggest that [123I]64 may be a new candidate tau-imaging agent.
- Matsumura, Kenji,Ono, Masahiro,Kitada, Ayane,Watanabe, Hiroyuki,Yoshimura, Masashi,Iikuni, Shimpei,Kimura, Hiroyuki,Okamoto, Yoko,Ihara, Masafumi,Saji, Hideo
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p. 7241 - 7257
(2015/10/05)
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- Photochemical direct perfluoroalkylation of phenols
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A metal-free photochemical strategy for the direct aromatic perfluoroalkylation of phenols is reported. This operationally simple approach occurs at ambient temperature and under illumination by a fluorescent light bulb. The chemistry is driven by the ability of phenolate anions, transiently generated upon deprotonation of phenols, to directly reach an electronically excited state upon light absorption while successively triggering the formation of reactive radical species from perfluoroalkyl iodides. Preliminary mechanistic studies are reported.
- Filippini, Giacomo,Nappi, Manuel,Melchiorre, Paolo
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supporting information
p. 4535 - 4542
(2015/06/08)
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- INHIBITORS TARGETING DRUG-RESISTANT INFLUENZA A
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Provided are compounds according to formula (la) or (lb) as described herein, that are capable of modulating the activity of influenza viruses (e.g., influenza A virus), for example, via interaction with the M2 transmembrane protein, and other similar viroporins. Also provided are methods for treating an influenza A-affected disease state or infection comprising administering a composition comprising one or more compounds according to according to formulas (la') or (lb), as described herein.
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Paragraph 0277
(2013/06/27)
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- Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents
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The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy)phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC50 = 190 nM and with cellular GI50 = 2100 nM, and 6-{2-[4-(2- dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC50 = 9 nM and GI50 = 220 nM.
- Niculescu-Duvaz, Dan,Niculescu-Duvaz, Ion,Suijkerbuijk, Bart M.J.M.,Ménard, Delphine,Zambon, Alfonso,Davies, Lawrence,Pons, Jean-Francois,Whittaker, Steven,Marais, Richard,Springer, Caroline J.
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p. 1284 - 1304
(2013/03/14)
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- Enantioselective intramolecular formal [2 + 4] annulation of acrylates and α,β-unsaturated imines catalyzed by amino acid derived phosphines
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The first chiral phosphine-catalyzed activation of acrylates for intramolecular formal [2 + 4] reactions with unsaturated imines is described. The catalytic reactions afford N-heterocycles with exceptionally high diastereo- and enantioselectivities. The [2 + 4] products are amenable for further transformations to useful molecules such as chiral piperidines and multicyclic structures.
- Jin, Zhichao,Yang, Ruojie,Du, Yu,Tiwari, Bhoopendra,Ganguly, Rakesh,Chi, Yonggui Robin
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supporting information; experimental part
p. 3226 - 3229
(2012/08/08)
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- Modulation on C- and N-terminal moieties of a series of potent and selective linear tachykinin NK2 receptor antagonists
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Herein we describe the synthesis of a series of new potent tachykinin NK2 receptor antagonists by the modulation of the Cand N-terminal moieties of ibodutant (MEN 15596, 1). The Nterminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C-terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK2 receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK2 receptor. Selected compounds were tested in vivo confirming their activity as NK2 antagonists. In particular, after both iv and id administration to guinea pig, compound 61b was able to antagonize NK2-induced colonic contractions with a potency and duration-of-action fully comparable to the reference compound 1 (MEN 15596, ibodutant).
- Gensini, Martina,Altamura, Maria,Dimoulas, Tula,Fedi, Valentina,Giannotti, Danilo,Giuliani, Sandro,Guidi, Antonio,Harmat, Nicholas J. S.,Meini, Stefania,Nannicini, Rossano,Pasqui, Franco,Tramontana, Manuela,Triolo, Antonio,Maggi, Carlo Alberto
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experimental part
p. 65 - 78
(2010/11/16)
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- PROCESSES FOR PRODUCTION OF 4-BIPHENYLYAZETIDIN-2-ONES
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The present invention relates to processes for the production of 4-biphenylylazetidin-2-one derivatives of formula (I).
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Page/Page column 40; 52
(2008/12/05)
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- Process For Production Of 4-Biphenylyazetidin-2-Ones
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The present invention relates to processes for the production of 4-biphenylylazetidin-2-one derivatives of formula
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Page/Page column 21
(2008/12/09)
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- Anti-hypercholesterolemic biaryl azetidinone compounds
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This invention provides cholesterol absorption inhibitors of Formula I: and the pharmaceutically acceptable salts thereof, wherein R12 is an alkyl, alkeny or alkynyl group mono- or poly-substituted with —OH, —COOH or a combination of —OH and —COOH, and R9 contains an alkyl, alkeny or alkynyl group substituted with a heterocyclic ring, amino or sulfonyl. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating atherosclerosis and preventing atherosclerotic disease events.
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Page/Page column 18
(2008/12/08)
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- Aminostyrylbenzofuran derivatives as potent inhibitors for Aβ fibril formation
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The synthesis of a novel series of aminostyrylbenzofuran derivatives 1a-w and their inhibitory activities for Aβ fibril formation were described. All the synthesized compounds were evaluated by thioflavin T (ThT) assay and displayed potent inhibitory activities for Aβ fibril formation. Among them, compounds 1i and 1q exhibited excellent inhibitory activities (IC50 = 0.07 and 0.08 μM, respectively) than those of Curcumin (IC50 = 0.80 μM) and IMSB (IC50 = 8.00 μM) as reference compounds. Both compounds were selected as promising candidates for further biological evaluation.
- Byun, Ji Hun,Kim, HyeYun,Kim, YoungSoo,Mook-Jung, Inhee,Kim, Dong Jin,Lee, Won Koo,Yoo, Kyung Ho
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scheme or table
p. 5591 - 5593
(2009/06/18)
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- PROCESSES FOR PRODUCTION OF PHENOLIC 4-BIPHENYLYLAZETIDIN-2-ONES
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The present invention relates to processes for the production of phenolic 4-biphenylylazetidin-2-one derivatives Formula (1)
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Page/Page column 35-36
(2010/11/24)
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- DIPHENYLHETEROCYCLE CHOLESTEROL ABSORPTION INHIBITORS
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Various azetidinone, pyrrolidine, imidazolidine, and oxazolidine derivatives are described, as are pharmaceutical compositions containing these compounds and methods of treatment of diseases using these compounds. Other embodiments are also described.
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Page/Page column 252-254; 275-276; 282-284
(2008/06/13)
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- 1,4-DIPHENYL-3-HYDROXYALKYL-2-AZETIDINONE DERIVATIVES FOR TREATING HYPERCHOLESTROLEMIA
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The invention relates to a chemical genus of 1,4-diphenyl-3-hydroxyalkyl-2-azetidinones useful for the treatment of hypercholesterolemia and related disorders, having general formula (I).
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Page/Page column 221
(2008/06/13)
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- BIPHENYLAZETIDINONE CHOLESTEROL ABSORPTION INHIBITORS
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The invention relates to a chemical genus of 4-biphenyl-1-phenylazetidin-2-ones useful in the treatment of hypercholesterolemia and other disorders. The compounds have the general formula (I). Pharmaceutical compositions and methods for treating cholesterol- and lipid-associated diseases are also disclosed.
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Page/Page column 181-182
(2008/06/13)
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- PHENYLAZETIDINONE DERIVATIVES
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Various azetidinone derivatives are described, as are pharmaceutical compositions containing these compounds and methods of treatment of diseases using these compounds. Other embodiments are also described.
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Page/Page column 249-250; 295; 299; 312-313
(2008/06/13)
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- A highly DNA-duplex-stabilizing metal-salen base pair
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Stabilizing influence: When a DNA duplex containing two salicylic aldehyde nucleosides facing each other is treated with ethylenediamine and one equivalent of a Cu2+ or Mn2+ salt, a metal-salen base pair is formed within the DNA. The resulting stabilization of the DNA structure is attributed to the cross-linking of the salicylic aldehyde units with ethylenediamine. (Chemical Equation Presented)
- Clever, Guido H.,Polborn, Kurt,Carell, Thomas
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p. 7204 - 7208
(2007/10/03)
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- Synthesis of regiospecifically substituted 2-hydroxybenzocyclobutenones
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Regiospecifically substituted 2-hydroxybenzocyclobutenones were synthesized from the corresponding TBS protected 2-bromo-mandelate esters via halogen-metal exchange, cyclization, and subsequent deprotection.
- Lear, Yvonne,Durst, Tony
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p. 817 - 824
(2007/10/03)
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- Use of conformationally restricted benzamidines as arginine surrogates in the design of platelet GPIIb-IIIa receptor antagonists
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The use of 5,6-bicyclic amidines as arginine surrogates in the design of a novel class of potent platelet glycoprotein IIb-IIIa receptor (GPIIb-IIIa) antagonists is described. The additional conformational restriction offered by the bicyclic nucleus results in 20-400-fold increases in potency compared to the freely flexible, acyclic benzamidine counterpart. The design, synthesis, structure-activity relationships (SAR), and in vitro activity of this novel class of GPIIb-IIIa antagonists are presented.
- Sall, Daniel J.,Arfsten, Ann E.,Bastian, Jolie A.,Denney, Michael L.,Harms, Cathy S.,McCowan, Jefferson R.,Morin Jr., John M.,Rose, Jack W.,Scarborough, Robert M.,Smyth, Mark S.,Um, Suzane L.,Utterback, Barbara G.,Vasileff, Robert T.,Wikel, James H.,Wyss, Virginia L.,Jakubowski, Joseph A.
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p. 2843 - 2857
(2007/10/03)
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- Binding of Phenylalkylamine Derivatives at 5-HT1C and 5-HT2 Serotonin Receptors: Evidence for a Lack of Selectivity
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Certain phenyalkylamine derivatives have been considered to bind selectively at 5-HT2 serotonin receptors.It is now recognized that the most widely used derivatives, i.e., 1-(2,5-dimethoxy-4-X-phenyl)-2-aminopropanes where X = Me (DOM), Br (DOB), and I (DOI) (1-3, respectively) also bind at the more recently identified population of serotonin 5-HT1C receptors.The purpose of the present investigation was to determine whether simple phenylalkylamines bind selectively at one population of receptors over the other.An examination of 34 derivatives reveals (i) similar structure-affinity relationships and (ii) a significant correlation (r = >0.9, n = 25) between 5-HT1C and 5-HT2 affinity.None of the compounds included in the present study displayed more than a 10-fold selectivity for one population of these receptors over the other; the results suggest that these compounds (including the widely used 5-HT2 agonists DOB and DOI) are 5-HT1C/5-HT2 agents.
- Glennon, Richard A.,Raghupathi, Reva,Bartyzel, Piotr,Teitler, Milt,Leonhardt, Sigrun
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p. 734 - 740
(2007/10/02)
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- 5-HT1 and 5-HT2 Binding Characteristics of 1-(2,5-Dimethoxy-4-bromophenyl)-2-aminopropane Analogues
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1-(2,5-Dimethoxy-4-bromophenyl)-2-aminopropane (DOB; 1a) is a purported serotonin (5-HT) agonist that binds selectively to central 5-HT2 binding sites.Systematic removal of any or all of the aromatic substituents had relatively little effect on 5-HT1 binding but reduced 5-HT2 binding by approximately 2 or more orders of magnitude.Demethylation of the 2-methoxy group of 1a, or introduction of N-n-propyl group, doubled 5-HT1-site affinity but decreased 5-HT2-site affinity by 3- and 30-fold, respectively.In tests of stimulus generalization, using rats trained to discriminate DOM from saline, the 2-demethyl and N-propyl derivatives were found to produce stimulus effects similar to those of DOB.In addition, the S-(+) isomer of the iodo analogue of 1a was found to possess one-third the affinity of its R-(-) enantiomer at 5-HT2 sites and also resulted in DOM-stimulus generalization.Of the DOB analogues examined, DOB (1a) possesses optimal selectivity for 5-HT2 binding.
- Glennon, Richard A.,McKenney, J. D.,Lyon, Robert A.,Titeler, Milt
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p. 194 - 199
(2007/10/02)
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