160127-75-3Relevant academic research and scientific papers
Biocatalytic Resolution of a Tertiary Quinuclidinol Ester Using Pig Liver Esterase
Coope, John F.,Main, Brian G.
, p. 1393 - 1398 (1995)
The kinetic resolution of a tertiary acetylenic ester has been accomplished using Pig liver esterase. (R) and (S) isomers of 3-ethynyl-3-hydroxy quinuclidine have been isolated with high enantiomeric purity.
N-ARYL-SUBSTITUTED CYCLIC AMINE DERIVATIVE AND MEDICINE CONTAINING THE SAME AS ACTIVE INGREDIENT
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Page 44, (2010/02/05)
The present invention provides an excellent squalene synthase inhibitor. Specifically, it provides a compound (I) represented by the following formula, a salt thereof or a hydrate of them. Wherein R1 represents an optionally substituted vinyl group or an aromatic ring which may be substituted; ???n is an integer of 0 to 2; ???X, Y and Z are the same as or different from each other and each represents an optionally substituted carbon atom, or an optionally substituted nitrogen a tom, sulfuratomoroxygenatom, and Y optionally represents a single bond, and when Y represents the single bond, the ring to which X, Y and Z belong is a 5-membered ring; ???CyA represents a 5- to 14 membered non-aromatic cyclic amino groupornon-aromatic cyclic amidogroupwhichmaybe substituted, and the non-aromatic cyclic amino group or the non-aromatic cyclic amido group optionally having an oxygen atom or a sulfur atom; ???W represents a chain expressed by(1) optionally substituted -CH2-CH2-,(2) optionally substituted -CH=CH-,(3) -C≡C-,(4) an optionally substituted phenylene group,(5) a single bond,(6) -NH-CO-,(7) -CO-NH-,(8) -NH-CH2-,(9) -CH2-NH-,(10) -CH2-CO-,(11) -CO-CH2-,(12) -O-(CH2)m-,(13) -(CH2)m-O- (where m represents an integer of 0 to 5),(14) -O-CH2-CR2=,(15) -O-CH2-CHR2- (where R2 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom),(16) -NH-S(O)1-,(17) -S(O)1-NH-,(18) CH2-S(O)1-, or(19) -S(O)2-CH2- (where 1 represents 0, 1, or 2); and ???A represents a group having any of the following structural formulae: (wherein R3 and R4 represent independently a hydrogen atom or an optionally substituted C1-6 alkyl group, or combine through a carbon chain optionally containing a heteroatom to form a ring; ???R5 and R6 represent independently a hydrogen atom or an optionally substituted C1-6 alkyl group, or combine through a carbon chain optionally containing a heteroatom to form a ring; ???R7 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, a hydroxyl group, an alkoxy group, a halogen atom or an optionally substituted amino group; ???R8 represents a hydrogen atom, a hydroxyl group, an alkoxy group, a halogen atom or an optionally substituted amino group; ???B1 represents an optionally substituted carbon atom, or an optionallysubstitutednitrogenatom, oxygen atom or sulfur atom; ???B2 represents an optionally substituted carbon atom or nitrogen atom; ???a and b represent an integer of 0 to 4, provided that a+b is an integer of 0 to 4; ???c represents 0 or 1; and----- represents a single bond or a double bond, provided that when c is 1 in which A is a quinuclidine having R8 represented by the case where R8 is a hydrogen atom or a hydroxyl group; Arl is an aromatic heterocycle; and W is one of (1) to (3), (6) to (11) and (16) to (19) are excluded).
Quinuclidine compounds and drugs containing the same as the active ingredient
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, (2008/06/13)
The present invention provides an excellent squalene synthesizing enzyme inhibitor. Specifically, it provides a compound (I) represented by the following formula, a salt thereof or a hydrate of them. In which R1 represents (1) hydrogen atom or (2) hydroxyl group; HAr represents an aromatic heterocycle which may be substituted with 1 to 3 groups; Ar represents an optionally substituted aromatic ring; W represents a chain represented by (1) —CH2—CH2— which may be substituted, (2) —CH=CH— which may be substituted, (3) —C≡C—, (4) —NH—CO—, (5) —CO—NH—, (6) —NH—CH2—, (7) —CH2—NH—, (8) —CH2—CO—, (9) —CO—CH2—, (10) —NH—S(O)l—, (11) —S(O)l—NH—, (12) —CH2—S(O)— or (13) —S(O)l—CH2— (l denotes 0, 1 or 2); and X represents a chain represented by (1) a single bond, (2) an optionally substituted C1-6 alkylene chain, (3) an optionally substituted C2-6 alkenylene chain, (4) an optionally substituted C2-6 alkynylene chain, (5) a formula —Q— (wherein Q represents oxygen atom, sulfur atom, CO or N(R2) (wherein R2 represents a C1-6 alkyl group or a C1-6 alkoxy group)), (6) —NH—CO—, (7) —CO—NH—, (8) —NH—CH2—, (9) —CH2—NH—, (10) —CH2—CO—, (11) —CO—CH2—, (12) —NH—S(O)m—, (13) —S(O)m—NH—, (14) —CH2—S(O)m—, (15) —S(O)m—CH2— (wherein m denotes 0, 1 or 2) or (16) —(CH2)n—O— (wherein n denotes an integer from 1 to 6).
Novel optimised quinuclidine squalene synthase inhibitors
Brown, George R.,Foubister, Alan J.,Freeman, Susan,McTaggart, Fergus,Mirrlees, Donald J.,Reid, Alan C.,Smith, Graham J.,Taylor, Melvyn J.,Thomason, Douglas A.,Whittamore, Paul R. O.
, p. 597 - 600 (2007/10/03)
Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3-ol 1c, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM) microsomal SQS; the oral ED50 of 1c, for the inhibition of rat cholesterol biosynthesis was 1.3 ± 0.45 mg/kg and for the R-enantiomer 1m, 0.8 ± 0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9 ± 0.25 mg/kg.
