28281-22-3

Upstream product

• 24123-89-5 (Z)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one 
• 108-86-1 bromobenzene 
• 5291-26-9 2-methylenequinuclidin-3-one 
• 100-52-7 benzaldehyde 
• 1193-65-3 3-quinuclidinone hydrochloride 
• 24123-89-5 2-benzylidene-3-quinuclidinone 
• 3731-38-2 3-Quinuclidinone 

Downstream Products

• 95556-22-2 2-(phenylmethyl)-1-azabicyclo<2.2.2>octane 
• 24177-82-0 2-benzyl-quinuclidin-3-ol 
• 40615-00-7 2-benzylquinuclidin-3-amine 
• 24177-82-0 (2S,3S)-2-benzylquinuclidin-3-ol 
• 147331-34-8 cis-2-(phenylmethyl)-N-<(2-methoxyphenyl)methyl>-1-azabicyclo<2.2.2>octan-3-amine 

Relevant academic research and scientific papers

Ruthenium-Catalyzed Highly Enantioselective Synthesis of cis-3-Quinuclidinols via DKR Asymmetric Transfer Hydrogenation

A method for the enantioselective synthesis of cis-3-quinuclidinols by Ru-catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution is described. The reaction proceeded under mild conditions using ammonium formate as the hydrogen donor, affording the products in high yields (up to 99%) with excellent diastereoselectivity (up to 99:1 dr) and enantioselectivity (95-99% ee). This protocol was applicable to gram-scale preparation with perfect enantioselectivity through simple recrystallization.

Overcoming chloroquine resistance in malaria: Design, synthesis and structure-activity relationships of novel chemoreversal agents

Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies.

2-(Arylmethyl)-3-substituted quinuclidines as selective α7 nicotinic receptor ligands

A series of 2-(arylmethyl)-3-substituted quinuclidines was developed as α7 neuronal nicotinic acetylcholine receptor (nAChR) agonists based on a putative pharmacophore model. The series is highly selective for the α7 over other nAChRs (e.g., the α4β2 of the CNS, and the muscle and ganglionic subtypes) and is functionally tunable at α7. One member of the series, (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan-2-carboxamide (+)-8l), has potent agonistic activity for the α7 nAChR (EC50 = 33 nM, Imax = 1.0), at concentrations below those that result in desensitization.

Substituted azabicyclic moieties for the treatment of disease

The invention provides compounds of Formula I: 1wherein m1 is 0 or 1; m2 is 1 or 2; R1 is —H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, or phenyl; R2 is —H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, or phenyl, provided that when m1 is 1 at least one of R1 and R2 is —H; or a pharmaceutically acceptable salt, pharmaceutical composition, a pure enantiomer or racemic mixture thereof. The invention also provides a method for treating a disease or condition in a mammal, wherein the α7 nicotinic acetylcholine receptor is implicated and for treating diseases where there is a sensory-gating deficit in a mammal comprising administering to a mammal a therapeutically effective amount of a compound of Formula I. These compounds may be in the form of pharmaceutical salts or compositions, and may be in pure enantiomeric form or may be racemic mixtures.

Exploring the stereoselectivity in the peterson reaction of several 2- substituted 1-azabicyclo[2.2.2]octan-3-ones

The Peterson reaction between a series of 2-substituted 1- azabicyclo[2.2.2]octan-3-ones and 3-methyl-5-trimethylsilanylmethyl isoxazole (1) was explored. (Z)-Stereoselectivity was obtained with all 2-substituents, ranging from 65:35 for benzyl to 95:5 for phenylsulphanyl. Different bases were investigated, revealing that an organolithium base is necessary for the reaction to occur. A transition state is suggested, involving a four-membered ring in which the lithium ion is covalently bound α to the silyl-group and chelated to the carbonyl oxygen. (C) 2000 Elsevier Science Ltd.

Toward an understanding of the high enantioselectivity in the osmium-catalyzed asymmetric dihydroxylation (AD). 1. Kinetics

A systematic study of the relationship between ligand structure and saturation rate constants (kc) in the amine-catalyzed osmylation of terminal olefins was carried out with the aim of learning more about the interactions between the reactants (i.e. OsO4, the ligand, and the olefin) and of establishing the origin of the large rate accelerations observed with cinchona alkaloid ligands. The results reveal that the saturation rate constants are influenced principally by the nature of the O9 substituent of the cinchona analogs studied, especially if aromatic substrates are used. Additionally, the binding constants (Keq) for OsO4 and the test ligands were measured, and the observed trends show that Keq can be regarded as an approximate measure of the steric hindrance in the vicinity of the ligand-binding site. Interestingly, the binding constants and the saturation rate constants kc are not correlated, indicating that the observed rate variations are apparently not caused by variations in ground-state energy due to steric interactions. Rather, the rate data can be interpreted in terms of a relative stabilization of the transition state of the reaction in the case of 'fast' ligands. A transition-state stabilization may result from stacking of the olefin and ligand substituents, and this theory is consistent with the fact that flat aromatic substrates give much higher rate constants than aliphatic ones. Further support for this theory was obtained from solvent effect and Hammett studies as well as from X-ray data on osmium glycolate complexes. Phthalazine ligand 1 gives exceptionally high rate constants with aromatic substrates, an effect which can be attributed to the presence of a 'binding pocket', set up by the phthalazine and methoxyquinoline moieties of the ligand, which enables especially good transition-state stabilization for aromatic olefins within the pocket. The enantioselectivity trends were found to parallel the rate trends; therefore, our results allow us to draw conclusions with regard to the mode of chirality transfer in the reaction, leading to a revised mnemonic device.

AZABICYCLIC COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE IN THERAPY

Compounds of formula (I), and salts and prodrugs thereof: STR1 wherein Q is the residue of an optionally substituted azabicyclic ring system;the dotted line represents an optional double bond;X represents H,--OH, =O or halo;R 1 represents H, phenyl or thienyl, which phenyl or thienyl groups may be optionally substituted by halo or trifluoromethyl; R 2 represents phenyl, thienyl or benzyl, any of which groups may be optionally substituted by halo or trifluoromethyl; andR 3, R 4 and R 5 independently represent H, C. sub.1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl,--OR a, SR a, SOR a, SO 2 R a,--NR a R b,--NR a COR b,--NR a CO 2 R. sup.b,--CO 2 R a or--CONR a R b ; andR a and R b independently represent H, C 1-6 alkyl, phenyl or trifluoromethyl, are tachykinin receptor antagonists. They and compositions thereof are useful in therapy.

Azabicyclic compounds as tachykinin antagonists

Compounds of formula (I), and salts and prodrugs thereof: ψψ ψwhereinψ Q is the residue of an optionally substituted azabicyclic ring system;ψ the dotted line represents an optional double bond;ψ X represents H, -OH, =O or halo;ψ R1 represents H, phenyl or thienyl, which phenyl or thienyl groups may be optionally substituted by halo or trifluoromethyl;ψ Ry represents phenyl, thienyl or benzyl, any of which groups may be optionally substituted by halo or trifluoromethyl; andψ R3, R4 and R5 independently represent H, C5±? alkyl, C6±? alkenyl, C6±? alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, -ORa, SRa, SORa, SO6Ra, -NRaRb, -NRaCORb, -NRaCO6Rb, -CO6Ra or -CONRaRb; andψ Ra and Rb independently represent H, C5±? alkyl, phenyl or trifluoromethyl, are tachykinin receptor antagonists. They and compositions thereof are useful in therapy.ψ