Tag: M.W=100-150

Kuroita, Takanobu; Marubayashi, Nobuhiro; Sano, Mitsuharu; Kanzaki, Kouji; Inaba, Kenichi; Kawakita, Takeshi published the artcile< Benzoxazines. II. Synthesis, conformational analysis, and structure-activity relationships of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide derivatives as potent and long-acting serotonin-3 (5-HT3) receptor antagonists>, SDS of cas: 120570-05-0, the main research area is serotonin antagonist antiemetic benoxazinecarboxamide analog preparation; structure activity serotonin antagonist benoxazinecarboxamide analog; conformation serotonin antagonist benoxazinecarboxamide analog preparation.

A series of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide derivatives was synthesized and evaluated for S3 serotonin (5-HT3) receptor antagonistic activities by means of assays of 5-HT3 receptor binding and the ability to antagonize the von Bezold-Jarisch reflex in rats. The target compounds were analogs and derivatives of (S)-N-1-azabicyclo[2.2.2]oct-3-yl-6-chloro-3,4-dihydro-4-methyl-2H-1,4-benzoxazine-8-carboxamide (I). Replacement of the 1,4-benzoxazine ring with a 1,4-benzthiazine ring or seven-membered ring (i.e., 1,5-benzoxepine or 1,5-benzthiepine) resulted in decreased affinity for 5-HT3 receptor. Introduction of substituents at the 2 position of the 1,4-benzoxazine ring increased the antagonistic activities (di-Me > Me > dihydro > phenyl). Compounds bearing a 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety as the basic part of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide derivatives were equipotent to those bearing 1-azabicyclo[2.2.2]oct-3-yl moiety. The 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety was confirmed to adopt a boat-chair conformation on the basis of both NMR studies and X-rays anal. In this series, endo-6-chloro-3,4-dihydro-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2,2,4-trimethyl-2H-1,4-benzoxazine-8-carboxamide showed the highest affinity for 5-HT3 receptors (Ki = 0.019 nM), and a long-lasting 5-HT3 receptor antagonistic activity as evidenced by antagonism to the von Bezold-Jarisch reflex in rats. Such a long-lasting 5-HT3 receptor antagonism would be attributed to the introduction of both two Me groups at the 2 position of the benzoxazine ring and the 9-methyl-9-azabicyclo[3.3.1]non-3-yl moiety, which adopted the boat-chair conformation.

Chemical & Pharmaceutical Bulletin published new progress about 5-HT3 antagonists. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, SDS of cas: 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Odzak, Renata; Primozic, Ines; Tomic, Srdanka published the artcile< 3-amidoquinuclidine derivatives: synthesis and interaction with butyrylcholinesterase>, Electric Literature of 120570-05-0, the main research area is aminoquinuclidine acid anhydride condensation; amidoquinuclidine preparation benzyl bromide alkylation; racemic enantiopure quaternary amidoquinuclidine preparation; butyrylcholinesterase inhibitor quaternary amidoquinuclidine.

Racemates as well as (R)- and (S)-enantiomers of 3-pivalamidoquinuclidine I (R = Me3C) and 3-acetamidoquinuclidine I (R = Me) were prepared Their quaternary racemic and enantiomerically pure N-benzyl derivatives II (R = Me3C, Me) were synthesized as well. I and II were tested as substrates and inhibitors of butyrylcholinesterase (BChE) from horse serum (EC 3.1.1.8). No hydrolysis was observed under the exptl. conditions applied. On the contrary, inhibition of BChE by (R)- and (S)-enantiomers of II (R = Me3C) was observed II (R = Me3C) with Ki = 41.57 μmol dm-3 was a 3-fold more potent inhibitor than the (R)-enantiomer. On the other hand, preliminary results indicated that both enantiomers of II (R = Me) may possibly be inhibitors as well as activators depending on the concentrations of benzoylcholine (BzCh) used as a substrate of BChE.

Croatica Chemica Acta published new progress about Amides 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, Electric Literature of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Youssefyeh, R. D.; Campbell, H. F.; Klein, S.; Airey, J. E.; Darkes, P.; Powers, M.; Schnapper, M.; Neuenschwander, K.; Fitzpatrick, L. R. published the artcile< Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure-activity relationship of novel benzamides>, Reference of 120570-05-0, the main research area is benzamide quinuclidinyl serotonin receptor antagonist; antiemetic quinuclidinyl benzamide.

Novel benzamides, e.g. I (X = H, Cl, Br, n = 1; X = Cl, n = 2), II (R = Me, Me2CHCH2, CH2:CHCHMe, MeCOCHMe), and S-III which are orally active, highly potent, specific antagonists of serotonin 5-HT3 receptors were prepared and the structure-activity relationships that led to these novel structures with improved potency in selectivity are described. (S)-III was identified and selected for further evaluation as a 5-HT3 receptor antagonist. Compared with 5-HT3 antagonists such as GR 38032F, BRL 43694, and metoclopramide, (S)-III was most active in (a) inhibiting binding to 5-HT3 receptor binding sites in rat entorhinal cortex with a Ki value of 0.19 nM and (b) blocking cisplatin-induced emesis in the ferret with an ED50 value determined to be 9 mg/kg, i.d.

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

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Masjedizadeh, Mohammad R.; Parnes, Howard published the artcile< Synthesis of the serotonin ligands, RS-56532-14C and RS-66331-14C from a common labeled intermediate>, Quality Control of 120570-05-0, the main research area is carbon labeled serotonin ligand; RS66331 carbon labeled; RS56532 carbon labeled; naphthalic anhydride intermediate labeled serotonin ligand.

Two approaches towards the synthesis of 3-chloro-4-amino-1,8-naphthalic anhydride-[14C] (I), which served as the common intermediate in the preparation of the two little compounds (II and III, resp.), are described. Although nucleophilic incorporation of the label via KCN was superior to an electrophilic sequence using CO2, the latter approach was adopted since the nitrile could not be hydrolyzed to the desired acid. The specific activities of RS-56532-14C and RS-66331-14C were 56.8 mCi/mmol and 53.7 mCi/mmol, resp.

Journal of Labelled Compounds and Radiopharmaceuticals published new progress about 120570-05-0. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Quality Control of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Dash, Jyotirmayee; Nath Das, Rabindra; Hegde, Nagaratna; Pantos, G. Dan; Shirude, Pravin S.; Balasubramanian, Shankar published the artcile< Synthesis of Bis-indole Carboxamides as G-Quadruplex Stabilizing and Inducing Ligands>, Computed Properties of 120570-05-0, the main research area is bisindolecarboxamide preparation G quadruplex stabilizing inducing ligand structure activity.

The design and synthesis of a series of bis-indole carboxamides with varying amine containing side chains as G-quadruplex DNA stabilizing small mols. are reported. For example, reacting amines R4NH2 [R4 = Me2N(CH2)3, pyrrolidino, 1-methyl-2-pyrrolidinyl, etc.] with bisindole diacid I (R = OH), which was prepared in 3 steps from 1,3-diethynylbenzene and Me 4-amino-3-iodobenzoate, gave carboxamides I (R = NHR4) in good yield. Their interactions with quadruplexes have been evaluated by means of Foerster resonance energy transfer (FRET) melting anal., UV/Vis spectroscopy, CD spectroscopy and mol. modeling studies. FRET anal. indicates that these ligands exhibit significant selectivity for quadruplex over duplex DNA, and the position of the carboxamide side chains is of paramount importance in G-quadruplex stabilization. UV/Vis titration studies reveal that bis-indole ligands bind tightly to quadruplexes and show a three- to five-fold preference for c-kit2 over h-telo quadruplex DNA. CD studies revealed that bis-indole carboxamide with a central pyridine ring induces the formation of a single, antiparallel conformation of the h-telo quadruplex in the presence and absence of added salt. The chirality of h-telo quadruplex was transferred to the achiral ligand (induced CD) and the formation of a preferred atropisomer was observed

Chemistry – A European Journal published new progress about DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (binding). 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

Burgi, Justus J.; Awale, Mahendra; Boss, Silvan D.; Schaer, Tifany; Marger, Fabrice; Viveros-Paredes, Juan M.; Bertrand, Sonia; Gertsch, Jurg; Bertrand, Daniel; Reymond, Jean-Louis published the artcile< Discovery of 3-benzylamino quinuclidones as potent positive allosteric modulators of the α3β2 nicotinic acetylcholine receptor by a chemical space walk in ChEMBL>, Reference of 120570-05-0, the main research area is pos allosteric modulator benzylaminoquinuclidone alpha3beta2 nicotinic receptor ChEMBL database; benzylaminoquinuclidone preparation nicotinic receptor PAM drug discovery.

While a plethora of ligands are known for the well studied α7 and α4β2 nicotinic acetylcholine receptor (nAChR), only very few ligands address the related α3β2 nAChR expressed in the central nervous system and at the neuromuscular junction. Starting with the public database ChEMBL organized in the chem. space of Mol. Quantum Numbers (MQN, a series of 42 integer value descriptors of mol. structure), a visual survey of nearest neighbors of the α7 nAChR partial agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282,987) pointed to N-(2-halobenzyl)-3-aminoquinuclidines as possible nAChR modulators. This simple “”chem. space walk”” was performed using a web-browser available at www.gdb.unibe.ch. Electrophysiol. recordings revealed that these ligands represent a new and to date most potent class of pos. allosteric modulators (PAMs) of the α3β2 nAChR, which also exert significant effects in vivo. The present discovery highlights the value of surveying chem. space neighbors of known drugs within public databases to uncover new pharmacol.

ACS Chemical Neuroscience published new progress about Allosterism. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Reference of 120570-05-0.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider

Clark, Robin D.; Miller, Aaron B.; Berger, Jacob; Repke, David B.; Weinhardt, Klaus K.; Kowalczyk, Bruce A.; Eglen, Richard M.; Bonhaus, Douglas W.; Lee, Chi Ho published the artcile< 2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists>, Recommanded Product: (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is quinuclidinyl pyridoindolone isoquinolinone preparation 5HT3 antagonist; pyridoindolone quinuclidinyl preparation 5HT3 antagonist; isoquinolinone quinuclidinyl preparation 5HT3 antagonist; receptor 5HT3 antagonist quinuclidinyl pyridoindolone isoquinolinone; indolone quinuclidinylpyrido preparation 5HT3 antagonist.

Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, pyrido[4,3-b]indol-1-one I (R = Me, R1 = H) and the 4,5-alkano-bridged analogs I [RR1 = (CH2)n (n = 3, 4)] displayed high 5-HT3 receptor affinity with pKi values >9. The (3S)-quinuclidinyl isomers had >10 fold higher affinity than the (3R)-isomers. In a series of 2-(quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (II; R = Me, Et, OMe, Cl, R1 = H) and with 4,5-alkano-bridges [II; RR1 = (CH2)n (n = 2, 3, 4)] also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 (III) was the highest affinity 5-HT3 receptor ligand prepared (pKi 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 μg/kg i.v.), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.

Journal of Medicinal Chemistry published new progress about 5-HT3 receptors Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Isik, Semra; Al Othman, Zeid; Osman, Sameh M.; Scozzafava, Andrea; Supuran, Claudiu T. published the artcile< Dithiocarbamates with potent inhibitory activity against the Saccharomyces cerevisiae β-carbonic anhydrase>, HPLC of Formula: 120570-05-0, the main research area is dithiocarbamate inhibitor selectivity Saccharomyces beta carbonic anhydrase; Saccharomyces cerevisiae; carbonic anhydrase; dithiocarbamate; inhibitor; β-Class enzyme.

Dithiocarbamates (DTCs) prepared from primary or secondary amines, which incorporated amino/hydroxyl-alkyl, mono-/bicyclic aliphatic/heterocyclic rings based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, were investigated for the inhibition of α- and β-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacol. relevance, such as the human (h) isoform hCA I and II, as well as the Saccharomyces cerevisiae β-CA, scCA. The yeast and its β-CA were shown earlier to be useful models of pathogenic fungal infections. The DTCs investigated here were medium potency hCA I inhibitors (KIs of 66.5-910 nM), were more effective as hCA II inhibitors (KIs of 8.9-107 nM) and some of them showed excellent, low nanomolar activity against the yeast enzyme, with inhibition constants ranging between 6.4 and 259 nM. The detailed structure activity relationship for inhibition of the yeast and human enzymes is discussed. Several of the investigated DTCs showed excellent selectivity ratios for inhibiting the yeast over the human cytosolic CA isoforms.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Carbonic anhydrase inhibitors. 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

Clark, R. D.; Muchowski, J. M.; Weinhardt, K. K.; Dillon, M. P.; Lee, C.-H.; Bley, K. R.; Bonhaus, D. W.; Wong, E. H. F.; Eglen, R. M. published the artcile< N-(Quinuclidin-3-yl)-2-(1-methyl-1H-indol-3-yl)-2-oxoacetamide: a high affinity 5-HT3 receptor partial agonist>, Name: (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is quinuclidinylindolyloxoacetamide enantiomer preparation serotoninergic receptor agonist; serotoninergic receptor partial agonist quinuclidinylindolyloxoacetamide enantiomer.

The enantiomers of the indolyl-2-oxoacetamide I were found to have 5-HT3 receptor partial agonist activity with (R)-I having higher potency than (S)-I.

Bioorganic & Medicinal Chemistry Letters published new progress about 5-HT3 agonists. 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

Lecoeur-Lorin, Marie; Delepee, Raphael; Morin, Philippe published the artcile< Sensitivity improvement by using contactless conductivity rather than indirect UV detection for the determination of enantiomeric purity of amines by CE>, Product Details of C7H14N2, the main research area is amine enantiomeric purity determination capillary electrophoresis contactless conductivity detection; crown compound selector amine capillary electrophoresis contactless conductivity detection; cyclodextrin derivative selector amine capillary electrophoresis contactless conductivity detection.

A capacitively coupled contactless conductivity detection (C4D) system for CE with a flexible detection cell was applied for the enantioseparation of small chiral underivatized amines using chiral crown ether or CD as chiral selector. Since these compounds are poorly UV-active, C4D was an alternative detection mode. The composition (ionic strength, pH, chiral selector) of the electrolyte was optimized to be suitable for C4D. (-)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid was required as chiral selector to resolve the enantiomers of small polar amines. However, trimethyl-β-CD was suitable to sep. amines possessing hydrophobic carbon chains. The performance of C4D was compared with indirect UV detection in terms of sensitivity, repeatability and accuracy. The linearity range of C4D was very large (1.5-1600 μg/mL) compared with the indirect UV linearity range (25-400 μg/mL) and allowed the determination of the enantiomeric purity of isopinocampheylamine up to 0.25%. The CE-C4D method was fully validated by applying a novel strategy using accuracy profiles. All relative biases of the developed method were included within the ±15% limits of acceptance. C4D is a good alternative to indirect UV detection for the enantioseparation of non-UV absorbing amines since the method development is fast and easy and, the sensitivity is improved by a factor of 100 compared with that of the indirect UV mode.

Electrophoresis published new progress about Amines Role: ANT (Analyte), ANST (Analytical Study). 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Product Details of C7H14N2.

Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider