2486-80-8Relevant academic research and scientific papers
Chlorination Reaction of Aromatic Compounds and Unsaturated Carbon-Carbon Bonds with Chlorine on Demand
Liu, Feng,Wu, Na,Cheng, Xu
supporting information, p. 3015 - 3020 (2021/05/05)
Chlorination with chlorine is straightforward, highly reactive, and versatile, but it has significant limitations. In this Letter, we introduce a protocol that could combine the efficiency of electrochemical transformation and the high reactivity of chlorine. By utilizing Cl3CCN as the chloride source, donating up to all three chloride atom, the reaction could generate and consume the chlorine in situ on demand to achieve the chlorination of aromatic compounds and electrodeficient alkenes.
Synthesis of 2-Methoxy-4-(methylsulfanyl)benzoic Acid — An Intermediate Product in the Preparation of the Cardiotonic Drugs Sulmazole and Isomazole
Lomov
, p. 1093 - 1098 (2019/10/19)
Readily available 4-methyl-3-nitrobenzenesulfonic acid and 2-methyl-5-nitrophenol were used to develop two alternative approaches to the synthesis of 2-methoxy-4-(methylsulfanyl)benzoic acid in total yields of 17% and 37%, respectively. The synthesis starting from 2-methyl-5-nitrophenol is more process-oriented and can be used in the resynthesis of Sulmazole and Isomazole.
Salicylic-acid derivatives as antennae for ratiometric luminescent probes based on lanthanide complexes
Terai, Takuya,Ito, Hiroki,Kikuchi, Kazuya,Nagano, Tetsuo
, p. 7377 - 7381 (2012/07/30)
Long-lived ratiometric sensors: Luminescent lanthanide complexes are widely used in time-resolved assays of biomolecules, but most of the sensors with these complexes rely on single-point intensity measurements. Herein, we introduce a simple strategy to create ratiometric probes by using salicylic-acid derivatives as the antenna moiety of Tb3+ complexes. As an example, a probe for alkaline phosphatase (ALP) was developed (see scheme). Copyright
Synthesis and evaluation of novel radioiodinated benzamides for malignant melanoma
Pham, Tien Q.,Greguric, Ivan,Liu, Xiang,Berghofer, Paula,Ballantyne, Patrice,Chapman, Janette,Mattner, Filomena,Dikic, Branko,Jackson, Timothy,Loc'h, Christian,Katsifis, Andrew
, p. 3561 - 3572 (2008/02/09)
The imaging potential of a series of [123I]benzamides was studied in mice bearing B16F0 melanoma tumors. Compound [123I]25 exhibited tumor uptake >8 %ID/g at 1 h, while that of [123I]14d and [123I]25 reached a maximum of 9-12 %ID/g at 6 h. Standardized uptake values of [123I]14d were higher than 100 between 24 and 72 h after injection. In haloperidol treated animals, the tumor uptake of [ 123I]14d was not significantly different to controls, while significant reduction of [123I]25 uptake was observed, supporting that [123I]14d uptake relates to melanin interaction, whereas part of the mechanism of [123I]25 uptake is related to its σ1-receptor affinity. Benzamides 14d and 25, which display rapid and high tumor uptake, appear to be promising imaging agents for melanoma detection, while 14d, which displays a long lasting and high melanoma/nontarget ratio, is more suitable for evaluation as a potential radiotherapeutic.
Indole-type derivatives as inhibitors of p38 kinase
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Page/Page column 69-70, (2008/06/13)
The invention is directed to methods to inhibit p38-α kinase using compounds comprising a phenyl or thienyl coupled through a piperidine or piperazine nucleus to an indole residue wherein the indole residue mandatorily has a substituent on the ring nitrogen which is an amino or substituted amino group.
NOVEL METHOXYBENZAMIDE COMPOUNDS FOR USE IN MCH RECEPTOR RELATED DISORDERS
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Page/Page column 50, (2010/02/07)
Novel compounds of Formula (I) which modulate MCH activity are disclosed, in which A is a linker; Ar1 is an aryl or heteroaryl group; R1 is a lower alkoxy group; R2 is an R1 group or hydrogen, an OH or an NH2 group, Q together with the carbonyl forms an amide group, which is further substituted with an amine group; R5 is selected from hydrogen, halogen atoms, alkoxy groups, hydroxy, alkylamino groups, dialkylamino groups, hydroxylalkyl groups, carboxamido groups, acylamido groups, acyl groups, -CHO, nitrile, alkyl, alkenyl or alkynyl groups, -SCH3, partially or fully fluorinated alkyl, alkoxy or thioalkoxy groups such as -CH2CF3, -CF2CF3, -CF3, -OCF3, -SCF3; -SO2NH2, -SO2NHAlk, -SO2NAlk2, -SO2Alk; X is H, F, Cl, Br, I, -SCH3, -CF3, -OCF3, -SCF3, OCH3, or lower alkyl or alkenyl group; R8 is halogen atoms, alkyl, alkenyl or alkynyl groups, cycloalkyl groups, aryl groups, heteroaryl groups, heterocyclyl groups, alkylcycloalkyl groups, alkylaryl groups, alkylheterocyclyl groups, alkylheteroaryl groups, arylalkoxy groups, aryloxy groups, alkoxy groups, dialkylamino groups, -CONHAlk, -CONHAr, -CONAlk2, -NHCO-Alk, -NHCO-Ar, -CO-Alk, -CO-Ar, -SCH3, partially or fully fluorinated alkyl, alkoxy or thioalkoxy groups; or R8 is R6-Ar2-B-, in which B is a single bond or a connecting moiety; Ar2 is an Ar1 group; R6 is an R5 group; and which are useful in the treatment or prevention of e.g. obesity, depression, diabetes, bulimia etc.
Synthesis and radiolabeling of (S)-4-amino-5-iodo-2-methoxy-N (1- azabicyclo[2.2.2]oct-3-yl)benzamide, the Active enantiomer of [125i]iodozacopride, and re-evaluation of its 5-HT3 receptor affinity
Hewlett, William A.,De Paulis, Tomas,Mason, N. Scott,Schmidt, Dennis E.,Trivedi, Bakula L.,Zhang, Zhang-Jin,Ebert, Michael H.
, p. 2079 - 2084 (2007/10/03)
We report an improved synthesis of unlabeled (S)-iodozacopride, the radiolabeling of (S)-[125I]iodozacopride via deschloro-(S)-zacopride, and a re-evaluation of its affinity for the 5-HT3 receptor. Unlabeled (S)- iodozacopride was prepared in seven steps from 4-aminosalicylic acid via alkaline hydrolysis of its 4-acetamide derivative. Catalytic hydrogenation of (S)-iodozacopride gave deschloro-(S)-zacopride, identical to that obtained from (S)-3-amino-quinuclidine and 4-amino-2-metihoxybenzoic acid via its corresponding 1-imidazole derivative. Radioiodination to produce (S)- [125I]iodozacopride was accomplished by treatment of deschloro-(S)- zacopride with 5mCi sodium 125iodide and chloramine-T in hydrochloric acid. Purification of the reaction products using an HPLC system capable of detecting chlorinated side-products revealed a mixture of 2.1 mCi (1.3nmol) (S)-[125I]iodozacopride and (S)-zacopride (1.5 nmol). Saturation analysis of the binding of the purified (S)-[125I]iodozacopride to whole rat brain homogenates gave an estimated K(D) of 1.10±0.07 nM. As anticipated, this is approximately haft the K(D) reported for binding of racemic [125I]iodozacopride, and differs from the previously reported value by an order of magnitude. Analysis of the apparent binding affinity of a 1: 1 mixture of (S)-[125I]iodozacopride and (S)-zacopride suggests that the previous result may have been confounded by contamination of the product with unlabeled (S)-zacopride. Competition analysis of the displacement of (S)- [125I]iodozacopride binding by unlabeled (S)-iodozacopride and (S)- zacopride gave K(i) values of 0.95 and 0.21 nM, respectively.
Preparation and in vitro pharmacology of 5-HT4 receptor ligands. Partial agonism and antagonism of metoclopramide analogous benzoic esters
Elz,Keller
, p. 585 - 594 (2007/10/03)
Alicyclic ester analogues of the gastroprokinetic benzamide metoclopramide (1) and its ester congener SDZ 205557 (2), a 5-HT4 receptor antagonist, were prepared by O-alkylation of 4-amino-5-chloro-2-methoxybenzoate with N-(2-chloroethyl) substituted alicyclic amines. The bromo and iodo analogue of compound 13b (2-(1-piperidinyl)ethyl 4-amino-5-chloro-2-methoxybenzoate) were obtained by halogenation of dechloro-13b with N-halogenated succinimides. The series was evaluated in functional in vitro assays with regard to affinity for serotoninergic 5-HT4, 5-HT3 and muscarinic M3 receptors. The affinities for 5-HT3 and M3 receptors were below 6.0 (pK(B) or pA2). On 5-HT4 receptors in guinea-pig ileal longitudinal muscle and rat oesophagus, the majority of compounds revealed partial 5-HT4 receptor agonism susceptible to blockade by SDZ 205557, a reference 5-HT4 receptor antagonist (pK(B) = 7.25-7.73 (guinea-pig ileum) and 7.09-7.43 (rat oesophagus)). The relative agonist potency was in the range of 5-303% (5-HT: 100%). Compound 13b and its bromo analogue 17 were the most potent esters of the series. The enantiomers of 13g ((R)- and (S)-2-(2-methyl-1-piperidinyl)ethyl 4-amino-5-chloro-2-methoxybenzoate) interacted stereoselectively with 5-HT4 receptors and displayed enantiomeric potency ratios (R)/(S) of 4.3-8.7. There was an excellent correlation between (a) antagonist affinity on guinea-pig ileum and rat oesophagus, (b) relative agonist potency on guinea-pig ileum and rat oesophagus, and (c) between antagonist affinity and relative agonist potency within each assay (r2 > 0.91). The new compounds may serve as academic tools in evaluating the functional role of 5-HT4 receptors. The selective partial 5-HT4 receptor agonists presented in this paper may be useful to restore physiological motility and secretion in the gut with reduced or absent propensity to elicit tachycardia and desensitization of the intestinal target receptor.
Inotropic activity of heterocyclic analogues of isomazole
Barraclough, P.,Beams, R. M.,Black, J. W.,Cambridge, D.,Collard, D.,et al.
, p. 467 - 477 (2007/10/02)
Aryl-substituted benzimidazole, imidazopyridine, imidazopyrazine, imidazopyridazine, oxazolopyridine, purine, pyrollopyridine and thiazolopyridine derivatives have been prepared and evaluated as inotropic agents.Purine 8 and the 1H-imidazo- and pyridazines 9 and 10 proved to be of most interest, having similar in vivo inotropic potencies to sulmazole.The pKa's, protonation sites and lipophilicities for most heterocycles were determined experimentally and some of their electronic properties calculated.For a subset of active heterocycles a correlation was observed between in vitro inotropism and the charge density of the imidazo nitrogen adjacent to the electrostatic potential minimum.Structure-activity relationships are discussed in some detail.
