- BF3·SMe2 for Thiomethylation, Nitro Reduction and Tandem Reduction/SMe Insertion of Nitrogen Heterocycles
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Herein, a general, solvent-free and straightforward thiomethylation of electron deficient heterocycles using BF3·SMe2 as a dual thiomethyl source and Lewis acidic activator is presented. A range of heterocycles including pyrimidine, pyrazine, pyridazine, thiazole and purine derivatives were successfully substituted using this method. An unexpected reductive property of BF3·SMe2 towards nitropyridines was also discovered including an intriguing tandem reduction/SMe insertion process in certain substrates. Notable features of the present work include its convenience and use of a non-malodorous reagent while the discovery of novel chemical transformations using BF3·SMe2 provides fundamental new insights into the reactivity of this commonly employed reagent.
- S?derstr?m, Marcus,Zamaratski, Edouard,Odell, Luke R.
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p. 5402 - 5408
(2019/06/27)
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- Α 7 as intranuclear hydroxynicotinic acetylcholine receptor quinuclidines compd.
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PROBLEM TO BE SOLVED: To provide ligands for the nicotinic α-7 receptor used for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.SOLUTION: The disclosure provides compounds of the specified formula I, including their salts, and compositions and methods using the compounds.
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Paragraph 0466; 0467
(2018/10/03)
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- Identification of RO4597014, a glucokinase activator studied in the clinic for the treatment of type 2 diabetes
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To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.
- Qian, Yimin,Corbett, Wendy L.,Berthel, Steven J.,Choi, Duk Soon,Dvorozniak, Mark T.,Geng, Wanping,Gillespie, Paul,Guertin, Kevin R.,Haynes, Nancy-Ellen,Kester, Robert F.,Mennona, Francis A.,Moore, David,Racha, Jagdish,Radinov, Roumen,Sarabu, Ramakanth,Scott, Nathan R.,Grimsby, Joseph,Mallalieu, Navita L.
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supporting information
p. 414 - 418
(2013/07/25)
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- Amido Compounds
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Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein the variables are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with the P2X7 purinergic receptor.
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Page/Page column 33
(2012/06/18)
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- NOVEL PHENYLPYRROLE DERIVATIVE
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The present invention relates to a compound or a pharmacologically acceptable salt thereof having superior glucokinase activating activity, and is a compound represented by general formula (I), or pharmacologically acceptable salt thereof: [wherein, A represents, for example, an oxygen atom or sulfur atom, R1 represents, for example, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 halogenated alkyl group, A and R1 together with the carbon atom bonded thereto form a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group α, R2 represents a phenyl group that may be substituted with 1 to 5 group(s) independently selected from Substituent Group α or a heterocyclic group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group α, R3 represents a hydroxy group or a C1-C6 alkoxy group, and Substituent Group α consists of, for example, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkyl group substituted with 1 or 2 hydroxy group(s), a C1-C6 alkylsulfonyl group, and a group represented by the formula -V-NR5R6 (wherein, V represents a carbonyl group or a sulfonyl group, and R5 and R6 may be the same or different and respectively represent a hydrogen atom or a C1-C6 alkyl group, or R5 and R6 together with the nitrogen atom bonded thereto form a 4- to 6-membered saturated heterocycle that may be substituted with 1 or 2 group(s) independently selected from a C1-C6 alkyl group and a hydroxy group, and the 4- to 6-membered saturated heterocycle may further contain one oxygen atom or nitrogen atom)].
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Page/Page column 131
(2010/11/03)
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- (IMIDAZOLO-5-YL)-2-ANILO-PYRIMIDINES AS AGENTS FOR THE INHIBITION OF CELL PROLIFERATION
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Compounds of the formula (I): wherein variable groups are as defined within and a pharmaceutically acceptable salts and in vivo hydrolysable esters are described. Also described are processes for their preparation and their use as medicaments, particularly medicaments for producing a cell cycle inhibitory (anti cell proliferation) effect in a warm blooded animal, such as man.
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Page/Page column 61
(2008/06/13)
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- 5-SUBSTITUTED-PYRAZINE OR PYRIDINE GLUCOKINASE ACTIVATORS
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The present invention provides a compound according to formula (I) where the substituent designations are provided in the specification. Pharmaceutical compositions comprising a compound according to formula (I) are also provided, said compounds being glucokinase activators which are useful in the treatment of type II diabetes.
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Page 85 - 86
(2010/02/07)
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- Heterocyclic indole derivatives and mono- or diazaindole derivatives
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There is provided a compound represented by the general formula (1): wherein Het represents an optionally substituted heterocyclic group; A1and A2each independently represent —CH═, etc.; A3represents —CH2—, etc.; R1represents a 4-fluorophenyl group, etc.; R2represents an alkyl group; n represents 0, 1 or 2, provided that when A1and A2both are —CH═, A3represents —CH2— or —SO2—, which is an indole derivative or a mono- or diazaindole derivative that has COX-2 inhibitory activity and is useful as a pharmaceutical, such as an anti-inflammatory agent, or addition salts thereof with a pharmaceutically acceptable acid or base, or hydrates thereof.
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Page column 60
(2008/06/13)
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- Heterocyclo-alkylsulfonyl pyrazole derivatives as anti-inflammatory/analgesic agents
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The present invention relates to compounds of the formula wherein R2, R3, R6and A are defined as in the specification, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the invention are useful in the treatment or alleviation of inflammation and other inflammation associated disorders, such as osteoarthritis, rheumatoid arthritis, colon cancer and Alzheimer's disease, in mammals (preferably humans, dogs, cats and livestock).
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- HETEROCYCLIC INDOLE DERIVATIVES AND MONO- OR DIAZAINDOLE DERIVATIVES
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Indole derivatives and mono- or diazaindole derivatives represented by general formula (1), pharmaceutically acceptable acid-addition salts or base-addition salts thereof or hydrates of the same which have a COX-2 inhibitory activity and are useful as drugs such as anti-inflammatory agents, wherein Het represents an optionally substituted heterocycle; A1 and A2 independently represent each -CH=, etc.; A3 represents -CH2-, etc.; R1 represents 4-fluorophenyl, etc.; R2 represents alkyl; and n is 0, 1 or 2, provided that when A1 and A2 are both -CH=, then A3 is -CH2- or -SO2-.
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