- Novel S1P1 receptor agonists - Part 2: From bicyclo[3.1.0] hexane-fused thiophenes to isobutyl substituted thiophenes
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Previously, we reported on the discovery of a novel series of bicyclo[3.1.0]hexane fused thiophene derivatives that serve as potent and selective S1P1 receptor agonists. Here, we discuss our efforts to simplify the bicyclohexane fused thiophene
- Bolli, Martin H.,Velker, J?rg,Müller, Claus,Mathys, Boris,Birker, Magdalena,Bravo, Roberto,Bur, Daniel,De Kanter, Ruben,Hess, Patrick,Kohl, Christopher,Lehmann, David,Meyer, Solange,Nayler, Oliver,Rey, Markus,Scherz, Michael,Steiner, Beat
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- Pichia stipitis OYE 2.6 variants with improved catalytic efficiencies from site-saturation mutagenesis libraries
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An earlier directed evolution project using alkene reductase OYE 2.6 from Pichia stipitis yielded 13 active site variants with improved properties toward three homologous Baylis-Hillman adducts. Here, we probed the generality of these improvements by testing the wild-type and all 13 variants against a panel of 16 structurally-diverse electron-deficient alkenes. Several substrates were sterically demanding, and as hoped, creating additional active site volume yielded better conversions for these alkenes. The most impressive improvement was found for 2-butylidenecyclohexanone. The wild-type provided less than 20% conversion after 24 h; a triple mutant afforded more than 60% conversion in the same time period. Moreover, even wild-type OYE 2.6 can reduce cyclohexenones with very bulky 4-substituents efficiently.
- Patterson-Orazem, Athéna,Sullivan, Bradford,Stewart, Jon D.
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p. 5628 - 5632
(2015/01/09)
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- Novel Pyridine Derivatives
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The invention relates to novel pyridine derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
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Page/Page column 11
(2009/01/24)
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- Hydrogenated Benzo (C) Thiophene Derivatives as Immunomodulators
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The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
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Page/Page column 23
(2008/12/07)
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- HYDROGENATED BENZO (C) THIOPHENE DERIVATIVES AS IMMUNOMODULATORS
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The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
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Page/Page column 62
(2010/11/24)
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- 1,2-Di(cyclic)substituted benzene compounds
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In one aspect, the present invention provides compounds having formula (1) or (100), a salt thereof or a hydrate of the foregoing, which compounds exhibit excellent cell adhesion inhibitory action or cell infiltration inhibitory action, and are useful as therapeutic or prophylactic agents for various inflammatory diseases and autoimmune diseases associated with adhesion and infiltration of leukocytes, such as inflammatory bowel disease (particularly ulcerative colitis or Crohn's disease), irritable bowel syndrome; rheumatoid arthritis, psoriasis, multiple sclerosis, asthma and atopic dermatitis. wherein R10 represents optionally substituted cycloalkyl, etc., R20-23 represent hydrogen, alkyl, alkoxy, etc., R30-32 represent hydrogen, alkyl, oxo, etc., and R40 represents optionally substituted alkyl, etc.
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Page/Page column 64
(2008/06/13)
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- Spiro compounds or salts thereof and preventives/remedies for autoimmune diseases and AP-1 inhibitors containing the same
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The spiro compounds of the present invention represented by the general formula: wherein A, R2, R3, R4, R5, R6and n are as defined in the specification, exhibit an AP-1 activity inhibitory action and, based on the AP-1 inhibitory action, suppresses the expression of a wide variety of genes and are useful as an agent for treating and preventing autoimmune diseases with lessoned side reactions.
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- Asymmetric Baeyer - Villiger oxidations of 4-mono- and 4,4-disubstituted cyclohexanones by whole cells of engineered Escherichia coli
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Whole cells of an Escherichia coli strain that overexpresses Acinetobacter sp. NCIB 9871 cyclohexanone monooxygenase have been used for the Baeyer-Villiger oxidations of a variety of 4-mono- and 4,4-disubstituted cyclohexanones. In cases where comparisons were possible, this new biocatalytic reagent provided lactones with chemical yields and optical purities that were comparable to those obtained from the purified enzyme or a strain of bakers' yeast that expresses the same enzyme. The efficient production of cyclohexanone monooxygenase in the E. coli expression system (ca. 30% of total soluble protein) allowed these oxidations to reach completion in approximately half the time required for the engineered bakers' yeast strain. Surprisingly, 4,4-disubstituted cyclohexanones were also accepted by the enzyme, and the enantioselectivities of these oxidations could be rationalized by considering the conformational energies of bound substrates along with the enzyme's intrinsic enantioselectivity. The enzyme expressed in E. coli cells also oxidized several 4-substituted cyclohexanones bearing polar substituents, often with high enantioselectivities. In the case of 4-iodocyclohexanone, the lactone was obtained in > 98% ee and its absolute configuration was assigned by X-ray crystallography. The crystal belongs to the monoclinic P21 space group with a = 5.7400(10), b = 6.1650(10), c = 11.377(2) A, b = 99.98(2)°, and Z = 2. Taken together, these results demonstrate the utility of an engineered bacterial strain in delivering useful chiral building blocks in an experimentally simple manner.
- Mihovilovic,Chen,Wang,Kyte,Rochon,Kayser,Stewart
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p. 733 - 738
(2007/10/03)
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