Category: quinuclidine

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

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

Sun, Ping; Armstrong, Daniel W. published the artcile< Effective enantiomeric separations of racemic primary amines by the isopropyl carbamate-cyclofructan6 chiral stationary phase>, Electric Literature of 120570-05-0, the main research area is primary amine enantioseparation HPLC isopropyl carbamate cyclofructan6 chiral phase; amino acid enantioseparation HPLC isopropyl carbamate cyclofructan6 chiral phase; alc amino enantioseparation HPLC isopropyl carbamate cyclofructan6 chiral phase.

A new chiral stationary phase (CSP) was developed by bonding isopropyl-carbamate functionalized cyclofructan6 (IP-CF6) to the silica gel. It was evaluated by injecting 119 racemic primary amine-containing compounds This CSP showed pronounced enantioselectivity toward all types of primary amines, separating 93% of all tested compounds Baseline separation was achieved even for some simple aliphatic racemic amines that contained no other functionality. The polar organic mode is the effective mobile phase owing to higher efficiency. This new chiral stationary phase showed great potential for preparative-scale separations It is also interesting that the chiral selector, R-naphthylethyl-carbamate functionalized CF6 (RN-CF6), provides complementary selectivity for the relatively few amine analytes that did not sep. on IP-CF6. Thus between the two CSPs, 98% of attempted amine compounds were separated

Journal of Chromatography A published new progress about Amino acid esters Role: ANT (Analyte), ANST (Analytical Study). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Electric Literature of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Mason, N. Scott; Hewlett, William A.; Ebert, Michael H.; Schmidt, Dennis E.; de Paulis, Tomas published the artcile< Labeling of (S)-des-4-amino-4-[125I]iodozacopride (DAIZAC), a high-affinity radioligand for the 5-HT-3 receptor>, Recommanded Product: (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is desaminoiodozacoprride iodine 125 preparation serotoninergic receptor.

We have prepared (S)-5-chloro-3-[125I]iodo-2-methoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)-benzamide ([125I]DAIZAC, [125I]-3) as a radioligand for characterization of the 5-HT-3 receptor. Preparation of the 3-tri-n-butylstannyl precursor was accomplished from the corresponding unlabeled DAIZAC by reaction with bis(tributyltin). Treatment of the precursor with 5 mCi of Na125I and chloramine-T in dilute HCl gave 2.58 ± 0.22 mCi (52%) of [125I]DAIZAC with >98% radiochem. purity and 1500 Ci/mmol specific activity. Saturation anal. of the binding of [125I]DAIZAC to rat brain homogenates showed a single binding site with a receptor d. Bmax of 0.66 ± 0.03 pmol/g and a receptor affinity KD of 0.15 ± 0.01 nM. Compared to [125I]iodozacopride, we find the 20-fold higher affinity and easy preparation of [125I]DAIZAC to be advantageous for in vitro identification of brain 5-HT-3 receptors.

Journal of Labelled Compounds & Radiopharmaceuticals published new progress about 5-HT3 receptors Role: ANT (Analyte), BSU (Biological Study, Unclassified), ANST (Analytical Study), BIOL (Biological Study). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Recommanded Product: (S)-3-Amino-1-azabicyclo[2.2.2]octane.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Hewlett, William A.; De Paulis, Tomas; Mason, N. Scott; Schmidt, Dennis E.; Trivedi, Bakula L.; Zhang, Zhang-Jin; Ebert, Michael H. published the artcile< 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>, Name: (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is iodozacopride radiolabeled preparation receptor affinity; HT3 receptor affinity radiolabeled iodozacopride.

Unlabeled (S)-iodozacopride was prepared in seven steps from 4-aminosalicylic acid via alk. hydrolysis of its 4-acetamide derivative Catalytic hydrogenation of (S)-iodozacopride gave dechloro-(S)-zacopride, identical to that obtained from (S)-3-aminoquinuclidine and 4-amino-2-methoxybenzoic acid via its corresponding 1-imidazole derivative Radioiodination to produce (S)-[125]iodozacopride was accomplished by treatment of dechloro-(S)-zacopride with 5 mCi 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 (1.3 nmol) (S)-[125I]iodozacopride and (S)-zacopride (1.5 nmol). Saturation anal. of the binding of the purified (S)-[125I]iodozacopride to whole rat brain homogenates gave an estimated KD of 1.10±0.07 nM. As anticipated, this is approx. half the KD reported for binding of racemic [125I]iodozacopride, and differs from the previously reported value by an order of magnitude. Anal. 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 anal. of the displacement of (S)-[125I]iodozacopride binding by unlabeled (S)-iodozacopride and (S)-zacopride gave Ki values of 0.95 and 0.21 nM, resp.

Chemical & Pharmaceutical Bulletin published new progress about 5-HT3 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Name: (S)-3-Amino-1-azabicyclo[2.2.2]octane.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Reed, J. Norm published the artcile< Product subclass 13: Benzyllithium compounds and (lithiomethyl)hetarenes>, Category: quinuclidine, the main research area is review benzyllithium derivative preparation organic synthesis.

A review of the preparation of benzylithium compounds and their applications to organic synthesis.

Science of Synthesis published new progress about Alkali metal organometallic compounds Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (benzyl). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Category: quinuclidine.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Kowalczyk, Bruce A. published the artcile< A short total synthesis of palonosetron using catalytic hydrogenation>, Synthetic Route of 120570-05-0, the main research area is total synthesis palonosetron.

The 5-HT3 receptor antagonists (I) and (II) (palonosetron) were synthesized by an efficient new route. The critical hydrogenation of imide III was carried out with either Pd/C catalyst or PtO2 catalyst.

Heterocycles published new progress about 120570-05-0. 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

Odzak, Renata; Tomic, Srdanka published the artcile< 3-Amidoquinuclidine derivatives: Synthesis of compounds and inhibition of butyrylcholinesterase>, Application of C7H14N2, the main research area is amidoquinuclidine preparation butyrylcholinesterase inhibition SAR.

The synthesis of racemic and enantiomerically pure 3-butanamidoquinuclidines ((±)-Bu, (R)-Bu and (S)-Bu), (1-3) and 3-benzamidoquinuclidines ((±)-Bz, (R)-Bz, and (S)-Bz), (4-6) is described. The N-quaternary derivatives, N-benzyl-3-butanamidoquinuclidinium bromides ((±)-BnlBu, (R)-BnlBu and (S)-BnlBu), (7-9) and N-benzyl-3-benzamidoquinuclidinium bromides ((±)-BnlBz, (R)-BnlBz and (S)-BnlBz), (10-12) were subsequently synthesized. The interaction of the four enantiomerically pure quaternary derivatives with horse serum butyrylcholinesterase (BChE) was tested. All tested compounds inhibited the enzyme. The best inhibitor of the enzyme was (S)-BnlBz with a K i = 3.7 μM. The inhibitor potency decreases in order (S)-BnlBz > (R)-BnlBz ≫ (R)-BnlBu > (S)-BnlBu.

Bioorganic Chemistry published new progress about Structure-activity relationship. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Application of C7H14N2.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Hewlett, William A.; Schmidt, Dennis E.; Mason, N. Scott; Trivedi, Bakula L.; Ebert, Michael H.; De Paulis, Tomas published the artcile< Synthesis and 5-HT3 receptor binding of 2- and 3-(halo)alkoxy substituted (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chlorobenzamides as potential radioligands>, Category: quinuclidine, the main research area is benzamide alkoxyazabicyclooctylhalo preparation 5HT3 receptor binding; receptor 5HT3 binding alkoxyazabicyclooctylhalobenzamide radioligand; azabicyclooctaneazabicyclooctane alkoxyhalobenzamido preparation 5HT3 receptor binding.

In an effort to develop selective, high-affinity radioligands for the 5-HT3 receptor, a series of homologs of 5-chloro-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide (I, R = Cl) was prepared in which individual methoxy groups were replaced by ethoxy, 2-fluoroethoxy, allyloxy, propargyloxy, or (3-iodoallyl)oxy groups. Affinities for the 5-HT3 receptor were determined by displacement of the binding of [125I]MIZAC (I, R = 125I), a selective 5-HT3 receptor antagonist radioligand, in rat brain homogenates. The 3-substituted homologs were more potent than the lead compound, I (R = Cl). The homolog having the largest 3-substituent, i.e., (E)-(S)-II (R = OCH2CH:CHI, R1 = OMe) (THIZAC), had one of the highest affinities, Ki 0.08 nM. The 2-substituted homologs were equipotent with I (R = Cl), having Ki 0.2-0.3 nM, regardless of the size of the substituent. The corresponding iodoallyl derivative, (E)-(S)-II (R = OMe, R1 = OCH2CH:CHI) (LIZAC), displayed a Ki of 0.29 nM. Saturation binding of [125I]-LIZAC gave a KD of 0.31 ± 0.04 nM and a Bmax of 2.36 ± 0.10 fmol/mg of entorhinal cortex. In vivo biodistribution of [125I]-LIZAC in the rat brain showed increased accumulation in hippocampus relative to that in cerebellum. Both the high-affinity ligands [125I]-THIZAC and [125I]-LIZAC are potentially useful radioligands for studying the 5-HT3 receptor.

Nuclear Medicine and Biology published new progress about 5-HT3 antagonists. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Category: quinuclidine.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

De Paulis, T.; Hewlett, W. A.; Schmidt, D. E.; Mason, N. S.; Trivedi, B. L.; Ebert, M. H. published the artcile< Synthesis and 5-HT-3 receptor binding activity of 5-[125I]iodo-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide and its 5-halogen-2-alkoxyl homologs>, COA of Formula: C7H14N2, the main research area is benzamide derivative serotonin receptor binding structure; azabicyclooctylbenzamide serotonin receptor binding structure; iodine labeling benzamide serotonin receptor binding; PET iodine labeled benzamide serotonin receptor; SPECT iodine labeled benzamide serotonin receptor.

(S)-5-Iodo-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide (MIZAC) was prepared from 5-iodo-2,3-dimethoxybenzoyl chloride and (S)-3-aminoquinuclidine. [125I]iodide-stannylation of its corresponding 5-tri-n-butyltin derivative gave [125I]-MIZAC at 1800 Ci/mmol. Binding of [125I]-MIZAC in rat entorhinal cortex revealed a KD of 1.37 nM. A series of racemic 2-O-alkyl derivatives of MIZAC were prepared and 5-HT-3 receptor affinities were determined by inhibition of [125I]-MIZAC binding. Optimal affinity for the receptor was obtained with small, electron-withdrawing substituents in the aromatic 5-position and with bulky substituents in the 3-position. [125I]-MIZAC is a selective radioligand useful for in vitro identification of the 5-HT-3 receptor. QSAR data suggest that potential candidates for SPECT and PET studies might be found in sterically bulky haloalkoxyl 5-chloro homologs of MIZAC.

European Journal of Medicinal Chemistry published new progress about 5-HT3 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, COA of Formula: C7H14N2.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider