- Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series
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Inhibition of stearoyl-CoA desaturase (SCD) activity represents a potential novel mechanism for the treatment of metabolic disorders including obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed SCD inhibitors, our research efforts have been focused on the search for new and structurally diverse liver-targeted SCD inhibitors. This work has led to the discovery of novel, potent and structurally diverse liver-targeted bispyrrolidine SCD inhibitors. These compounds possess suitable cellular activity and pharmacokinetic properties to inhibit liver SCD activity in a mouse pharmacodynamic model.
- Lachance, Nicolas,Gareau, Yves,Guiral, Sebastien,Huang, Zheng,Isabel, Elise,Leclerc, Jean-Philippe,Leger, Serge,Martins, Evelyn,Nadeau, Christian,Oballa, Renata M.,Ouellet, Stephane G.,Powell, David A.,Ramtohul, Yeeman K.,Tranmer, Geoffrey K.,Trinh, Thao,Wang, Hao,Zhang, Lei
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scheme or table
p. 980 - 984
(2012/03/26)
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- NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
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Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and
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Page/Page column 47; 50
(2011/02/24)
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- HETEROCYCLIC DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
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Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R1— substituted heteroaryl, R1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N—CR5R6, C═CR5 or CR13—CR5R6, Y is a bond or —C(O)—, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.
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Page/Page column 43
(2011/12/14)
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- HETEROCYCLIC DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
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Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R1-substituted heteroaryl, R1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N-CR5R6, C=CR5 or CR13-CR5R6, Y is a bond or -C(O)-, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.
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Page/Page column 68
(2010/09/17)
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- NOVEL SPIRO COMPOUNDS USEFUL AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
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Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desat- urase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.
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Page/Page column 60
(2010/09/17)
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- HETEROCYCLIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
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Heterocyclic compounds of structural formula I are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD). The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease; atherosclerosis; obesity; diabetes; neurological disease; Metabolic Syndrome; insulin resistance; cancer, liver steatosis; and non-alcoholic steatohepatitis.
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Page/Page column 51
(2010/11/03)
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- DIPEPTIDYL PEPTIDASE IV INHIBITOR
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A compound represented by general formula (I):A-B-D whereinA represents a substituted or unsubstituted 1-pyrrolidinyl group, a substituted or unsubstituted 3-thiazolidinyl group, a substituted or unsubstituted 1-oxo-3-thiazolidinyl group, or the like;B r
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Page/Page column 71-72
(2010/11/29)
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