Heterocyclic Building Blocks-Quinuclidine

Youssefyeh, Raymond D.; Campbell, H. F.; Airey, J. E.; Klein, S.; Schnapper, M.; Powers, M.; Woodward, R.; Rodriguez, W.; Golec, S. published the artcile< Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides>, Related Products of 120570-05-0, the main research area is serotoninergic S3 antagonist tricyclic benzamide; quinuclidinylaminocarbonyl dibenzofuran derivative preparation antiemetic.

Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog. The absolute configuration of the most active mols. I and II have been determined by x-ray crystallog. These two compounds are more potent than known 5-HT3 receptor antagonists both in vivo and in vitro in blocking 5-HT3 receptor activation and preventing chemotherapeutic induced emesis. Compared with 5-HT3 antagonists, such as GR 38032F, zacopride, BRL 43694, and ICS 205-930, I was more potent in (1) inhibiting binding to 5-HT3 receptor binding sites in rat cortex (Ki = 0.17 nM), (2) blocking the von Bezold-Jarisch effect in the rat (lowest ED, 1 μg/kg i.v.), and (3) inhibiting 5-HT-induced contraction of guinea pig ileum (lowest effective concentration, 10-9 M). This novel agent was as effective given orally as when given i.v. in reducing cisplatin-induced emetic episodes in the ferret (ED50 = 4 μg/kg i.v. or orally). A 1 mg/kg oral dose of I virtually abolished cisplatin-induced emesis for 10 h in the ferret. However, it was inactive against apomorphine or copper sulfate-induced vomiting. These data, coupled with receptor binding studies of ligands for D2-dopamine, a1, a2, 5-HT1, 5-HT2, and muscarinic receptors demonstrate that II is a highly selective 5-HT3 receptor antagonist with remarkable potency in vivo.

Journal of Medicinal Chemistry published new progress about 5-HT3 antagonists. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Related Products of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Kowalczyk, Bruce A.; Dvorak, Charles A. published the artcile< Total synthesis of the 5-HT3 receptor antagonist palonosetron>, Application of C7H14N2, the main research area is palonosetron 5HT3 receptor antagonist total synthesis.

A short and efficient synthetic route to the 5-HT3 receptor antagonists RS-42358-159 (I) and palonosetron was developed starting from 1,8-naphthalic anhydride. The novel adjustment of the oxidation states at the necessary centers of imide II (RR1, R2R3 = bond; R4R5 = O) was accomplished by hydrogenation, selective NaBH4 reduction, and dehydration to yield I. The NaBH4 reduction of imide II (R, R1, R2, R3 = H; R4R5 = O) was selective for the C(3) carbonyl vs. the C(1) carbonyl next to the aromatic ring to give the hydroxy compound II (R, R1, R2, R3, R4 = H; R5 = OH). It was essential to keep the NaBH4 reduction free of O, or diols were formed as byproducts.

Synthesis published new progress about 120570-05-0. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Application of C7H14N2.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Clark, R. D.; Weinhardt, K. K.; Berger, J.; Lee, C. H.; Leung, E.; Wong, E. H. F.; Smith, W. L.; Eglen, R. M. published the artcile< N-(Quinuclidin-3-yl)-1,8-naphthalimides with 5-HT3 receptor antagonist and 5-HT4 receptor agonist properties>, Computed Properties of 120570-05-0, the main research area is quinuclidinylnaphthalimide 5HT receptor antagonist agonist; naphthalimide quinuclidinyl.

The enantiomers of N-(quinuclidin-3-yl)-4-amino-3-chloro-1,8-naphthalimide (I) were preparation and examined for interactions at 5-HT3 and 5-HT4 receptors. (R)-I was a potent 5-HT3 receptor antagonist while (S)-I was a 5-HT4 receptor agonist with reduced 5-HT3 receptor affinity.

Bioorganic & Medicinal Chemistry Letters published new progress about 5-HT4 agonists. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Computed Properties of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Ouach, Aziz; Pin, Frederic; Bertrand, Emilie; Vercouillie, Johnny; Gulhan, Zuhal; Mothes, Celine; Deloye, Jean-Bernard; Guilloteau, Denis; Suzenet, Franck; Chalon, Sylvie; Routier, Sylvain published the artcile< Design of α7 nicotinic acetylcholine receptor ligands using the (het)Aryl-1,2,3-triazole core: Synthesis, in vitro evaluation and SAR studies>, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is triazole quinuclidinyl preparation alpha7 nicotinic acetylcholine receptor ligand; Alpha 7 nicotinic acetylcholine receptors; In vitro evaluation; Quinuclidine; SAR; Triazole synthesis; Tropane.

We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as α7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for α7 nAchR such as a (R)-quinuclidine configuration and a mono C-3 quinuclidine substitution. The triazole ring was substituted by a Ph ring bearing small OMe/CH2F groups or fluorine atom and by several heterocycles such as thiophenes, furans, benzothiophenes, or benzofurans. Among the 30 derivatives tested, the two derivatives I and II with Ki in the nanomolar range were identified (2.3 and 3 nM resp.). They exhibited a strict selectivity toward the α4β2 nicotinic receptor (up to 1 μM) but interacted with the 5HT3 receptors with Ki around 3 nM. Synthesis, SAR studies, and a full description of the derivatives are reported.

European Journal of Medicinal Chemistry published new progress about Alkynes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Lopez-Rodriguez, Maria L.; Benhamu, Bellinda; Morcillo, M. Jose; Tejada, Ignacio D.; Orensanz, Luis; Alfaro, M. Jose; Martin, M. Isabel published the artcile< Benzimidazole Derivatives. 2. Synthesis and Structure-Activity Relationships of New Azabicyclic Benzimidazole-4-carboxylic Acid Derivatives with Affinity for Serotoninergic 5-HT3 Receptors>, Application In Synthesis of 120570-05-0, the main research area is benzimidazole preparation structure serotoninergic receptor ligand; serotonin 5HT3 antagonist benzimidazole derivative structure.

A new series of azabicyclic benzimidazole-4-carboxamides and -carboxylates were synthesized and evaluated for binding affinity at serotoninergic 5-HT3 and 5-HT4 receptors in the CNS. Most of the synthesized compounds exhibited high or very high affinity for the 5-HT3 binding site and low to no significant affinity for the 5-HT4 receptor. SAR observations indicated that a halogen atom at the 6-position and a nitro group at the 7-position of the benzimidazole ring is the best substitution pattern for 5-HT3 affinity and 5-HT3/5-HT4 selectivity, as well as no substitution in this ring. Three (S)-(-)-N-(quinuclidin-3-yl)benzimidazole-4-carboxamides bound at central 5-HT3 sites with high affinity (Ki = 2.6, 0.13, and 1.7 nM, resp.) and excellent selectivity over serotonin 5-HT4 and 5-HT1A receptors (Ki > 1000-10000 nM). Furthermore, these new 5-HT3 receptor ligands were pharmacol. characterized as potent and selective 5-HT3 antagonists in the isolated guinea pig ileum (pA2 = 9.6, 9.9, and 9.1, resp.).

Journal of Medicinal Chemistry published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Application In Synthesis of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Glor, Ethan C.; Blau, Samuel M.; Yeon, Jeongho; Zeller, Matthias; Shiv Halasyamani, P.; Schrier, Joshua; Norquist, Alexander J. published the artcile< [R-C7H16N2][V2Te2O10] and [S-C7H16N2][V2Te2O10]; new polar templated vanadium tellurite enantiomers>, Synthetic Route of 120570-05-0, the main research area is polar vanadium tellurite enantiomer ammonioquinuclidine template hydrothermal preparation; crystal structure polar vanadium tellurite enantiomer ammonioquinuclidine template; stereoactive lone pair polar vanadium tellurite enantiomer ammonioquinuclidine template; dipole moment polar vanadium tellurite enantiomer ammonioquinuclidine template; charge distribution polar vanadium tellurite enantiomer ammonioquinuclidine template; second harmonic generation polar vanadium tellurite enantiomer ammonioquinuclidine template.

New polar vanadium tellurite enantiomers were synthesized under mild hydrothermal conditions through the use of sodium metavanadate, sodium tellurite and enantiomerically pure sources of either (R)-3-ammonioquinuclidine or (S)-3-ammonioquinuclidine. [R-C7H16N2][V2Te2O10] and [S-C7H16N2][V2Te2O10] contain [V2Te2O10]n2n- layers constructed from [(VO2)2O(TeO4)2] monomers. Steric effects associated with the H-bonding network between the [V2Te2O10]n 2n- layers and [C7H16N2]2+ result in polar structures and crystallization in the space group P21. Electron localization functions were calculated to visualize the tellurite stereoactive lone pairs. Both iterative and noniterative Hirshfeld techniques were evaluated as means to determine at. partial charges, with iterative Hirshfeld charges more accurately representing charge distributions in the reported enantiomers. These charges were used to calculate both component and net dipole moments. [R-C7H16N2][V2Te2O10] and [S-C7H16N2][V2Te2O10] exhibit dipole moments of 17.37 and 16.62 D, resp. [R-C7H16N2][V2Te2O10] and [S-C7H16N2][V2Te2O10] both display type 1 phase-matching capabilities and exhibit second harmonic generation activities of ∼50 × α-SiO2.

Journal of Solid State Chemistry published new progress about Dipole moment. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Synthetic Route of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Kuroita, Takanobu; Sakamori, Masamitsu; Kawakita, Takeshi published the artcile< Design and synthesis of 6-chloro-3,4-dihydro-4-methyl-2H-1,4-benzoxazine-8-carboxamide derivatives as potent serotonin-3 (5-HT3) receptor antagonists>, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is benzoxazinecarboxamide preparation serotonin receptor antagonist.

Several 3-substituted 5-chloro-2-methoxybenzamides I (R1 = NMe2, NH2, NMeCOMe) were synthesized and evaluated for serotonin-3 (5-HT3) receptor binding affinity. The 5-HT3 receptor antagonistic activity of zacopride, a representative 5-HT3 receptor antagonist, was unchanged by the replacement of the 4-amino substituent on the aromatic moiety by a 3-dimethylamino substituent. This finding promoted a structural modification of azasetron, another 5-HT3 receptor antagonist. Consequently, a new series of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamides II (R2 = H, Me, Et, Pr, CH2Ph, COPh, etc., R3 = Cl; R2 = Me, R3 = F, Br, Me, NO2, NH2, H) was obtained and these compounds were found to be more potent than 3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxamides. In particular, (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-3,4-dihydro-4-methyl-2H-1,4-benzoxazine-8-carboxamide showed a high affinity for 5-HT3 receptors (K = 0.051 nM) and especially potent antagonistic activity against the von Benzold-Jarisch reflex (ED50 = 0.089 μg/kg i.v.) in rats.

Chemical & Pharmaceutical Bulletin published new progress about 5-HT3 antagonists. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Gong, Leyi; Parnes, Howard published the artcile< Synthesis of the 3H-labeled 4-HT3 antagonist (RS-25259-197) at high specific activity>, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is RS 25259 197 tritium label preparation; tritiation RS 25259 197.

The preparation of the title compound, a selective 5-HT3 antagonist with antiemetic properties, was described. The key intermediate was 6-bromo-1,2-dihydronaphthoic acid, which was synthesized from 4-bromophenylacetic acid by Michael addition, acid-induced ring cyclization, reduction and dehydration. The compound 6-bromo-1,2-dihydronaphthoic acid was selected because it has two labeling sites to ensure high specific activity of the final product. Reduction of 6-bromo-1,2-dihydronaphthamide with carrier-free tritium gas, followed by reduction of the amide functional group with BF3-OEt2 and intramol. cyclization furnished the title compound having a specific activity of 70.4 Ci/mmol and >99% purity.

Journal of Labelled Compounds & Radiopharmaceuticals published new progress about Tritiation. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Akdemir, Atilla; Isik, Semra; Lanzi, Cecilia; Scozzafava, Andrea; Masini, Emanuela; Supuran, Claudiu T. published the artcile< Synthesis of a new series of dithiocarbamates with effective human carbonic anhydrase inhibitory activity and antiglaucoma action>, HPLC of Formula: 120570-05-0, the main research area is dithiocarbamate preparation carbonic anhydrase inhibitory activity antiglaucoma anticancer; Antiglaucoma; Carbonic anhydrase; Dithiocarbamate; Intraocular pressure.

A new series of dithiocarbamates (DTCs) was prepared from primary/secondary amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, and carbon disulfide. The compounds were investigated for the inhibition of four mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacol. relevance, i.e., the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient hCA I inhibitors (off-target isoform for both applications), efficiently inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering properties in an animal model of glaucoma, with a two times better efficiency compared to the clin. used sulfonamide dorzolamide.

Bioorganic & Medicinal Chemistry published new progress about Antiglaucoma agents. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, HPLC of Formula: 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Meng, Genyi; Guo, Taijie; Ma, Tiancheng; Zhang, Jiong; Shen, Yucheng; Sharpless, Karl Barry; Dong, Jiajia published the artcile< Modular click chemistry libraries for functional screens using a diazotizing reagent>, Product Details of C7H14N2, the main research area is alkyl aryl azide triazole chemoselective preparation; fluorosulfonyl azide generation chemoselective diazotization primary amine; combinatorial generation library alkyl aryl azide cycloaddition alkyne; functional screen click chem azide generated in situ.

Alkyl and aryl azides were prepared from the corresponding primary alkyl and aryl amines by reaction with fluorosulfonyl azide generated in situ from a fluorosulfonylimidazolium triflate and sodium azide, expanding access to azides and both to the 1,2,3-triazoles derived from them and to functional screens employing them. The method allowed the preparation of a library of >1000 azides from the corresponding amines; the azide library underwent copper-catalyzed azide-alkyne cycloaddition reactions to yield a library of >1000 1,2,3-triazoles.

Nature (London, United Kingdom) published new progress about Alkyl azides Role: CMB (Combinatorial Study), RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Product Details of C7H14N2.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider