ChemInform Abstract: SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF ANALOGS OF OXAPADOL, A NEW ANALGESIC AGENT

Dostert, P.; Langlois, Michel; Guerret, Patrick; Ancher, J. F.; Bucher, Brian T.; Mocquet, G.

doi:10.1002/chin.198043241

Cited by 3 publications

(3 citation statements)

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“…Enantiomerically pure (S)-1,2-O-isopropylidene-5-O-(methylsulfonyl)pentane-1,2,5-triol (18) [25] was obtained from L-glutamic acid in four steps. L-Glutamic acid was converted to (S)-2,3,4,5-tetrahydro-5-oxofuran-2-carboxylic acid as described by Herdeis [26].…”

Section: Methodsmentioning

confidence: 99%

Intercalating Nucleic Acids Containing Insertions of Naphthalimide

Wamberg¹,

Walczak²,

Andersen³

et al. 2006

HCA

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In a study of linker-length dependence, we evaluated naphthalimide (= 1H-benzo [de]isoquinoline-1,3(2H)-dione) and 4-bromonaphthalimide as intercalating nucleic acids. We used a vicinal dihydroxy system when incorporating the six different naphthalimide monomers into DNA, and found the minimum linker-length to be five C-atoms. With this length of the linker, naphthalimide was discriminating between DNA and RNA -stabilizing DNA, while destabilizing RNA. Furthermore, naphthalimide showed universal base character by hybridizing to the four natural bases with a range as narrow as 1.48. When compared to pyrene, naphthalimide with the same linker-length gave significantly higher thermal meltings when hybridized to DNA.

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Section: Methodsmentioning

confidence: 99%

Intercalating Nucleic Acids Containing Insertions of Naphthalimide

Wamberg¹,

Walczak²,

Andersen³

et al. 2006

HCA

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“…Oxapadol ( 282 ) is a non-narcotic analgesic that demonstrated activity in models of pain conducted in mice, rats, and rabbits, providing the basis of advancement into clinical trials which occurred in the late 1970s . SAR studies indicated that the dioxolane ring and its relationship and connectivity with the benzimidazole were of importance to the expression of pharmacological activity, which was assessed by screening for analgesic activity in mice as protection against phenylbenzoquinone-induced writhing .…”

Section: Introductionmentioning

confidence: 99%

Geminal Diheteroatomic Motifs: Some Applications of Acetals, Ketals, and Their Sulfur and Nitrogen Homologues in Medicinal Chemistry and Drug Design

Meanwell

2021

J. Med. Chem.

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Acetals and ketals and their nitrogen and sulfur homologues are often considered to be unconventional and potentially problematic scaffolding elements or pharmacophores for the design of orally bioavailable drugs. This opinion is largely a function of the perception that such motifs might be chemically unstable under the acidic conditions of the stomach and upper gastrointestinal tract. However, even simple acetals and ketals, including acyclic molecules, can be sufficiently robust under acidic conditions to be fashioned into orally bioavailable drugs, and these structural elements are embedded in many effective therapeutic agents. The chemical stability of molecules incorporating geminal diheteroatomic motifs can be modulated by physicochemical design principles that include the judicious deployment of proximal electron-withdrawing substituents and conformational restriction. In this Perspective, we exemplify geminal diheteroatomic motifs that have been utilized in the discovery of orally bioavailable drugs or drug candidates against the backdrop of understanding their potential for chemical lability.

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“…Anal. (C12H24N2O4) C,H,N.4-(4-Ethoxycarbonylpiperazinylethyl)-2,2-dimethyl-(1,3)-dioxolane (62).To a stirred mixture of 80.0 g (0.35 mol) of 4-methylsulfonylmethyl-2,2-dimethyl-(1,3)-dioxolane,48 48.4 g (0.35 mol) of potassium carbonate and 400 mL of dry toluene, under nitrogen, was added dropwise 55.53 g (0.35 mol) 4-ethoxycarbonylpiperazine at ambient temperature. The mixture was refluxed for 17 h, cooled, filtered and the salt cake washed with three 150-mL portions of toluene.…”

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confidence: 99%

Behavioral Approach to Nondyskinetic Dopamine Antagonists: Identification of Seroquel

et al. 2001

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A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias whereas its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.

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ChemInform Abstract: SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF ANALOGS OF OXAPADOL, A NEW ANALGESIC AGENT

Abstract: Zahlreiche Derivate des neuen Analgeticums Oxapadol (IIIa) werden synthetisiert.

Cited by 3 publications

References 0 publications

Intercalating Nucleic Acids Containing Insertions of Naphthalimide

Intercalating Nucleic Acids Containing Insertions of Naphthalimide

Geminal Diheteroatomic Motifs: Some Applications of Acetals, Ketals, and Their Sulfur and Nitrogen Homologues in Medicinal Chemistry and Drug Design

Behavioral Approach to Nondyskinetic Dopamine Antagonists: Identification of Seroquel

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