- Synthesis of β-dimethylsulfonium- and β-methylthio-substituted vinyl triflates by reaction of acetylenes with dimethyl sulfide ditriflate
-
A one-pot synthesis of β-dimethylsulfonium-substituted vinyl triflates by the reaction of dimethyl sulfide ditriflate with acetylenes is described. β-Dimethylsulfonium-substituted vinyl triflates were found to exhibit unusual reactivity towards nucleophil
- Nenajdenko, Valentine G.,Vertelezkij, Pavel V.,Balenkova, Elizabeth S.
-
-
Read Online
- SULFINIC ACID COMPOUNDS AS FREE FATTY ACID RECEPTOR AGONISTS
-
The present invention relates to certain compounds, their use in therapy, as well as to pharmaceutical compositions including said compounds. Specifically, the invention relates to certain compounds and pharmaceutical compositions including these compounds for the treatment of metabolic disorders including, for example, diabetes, obesity, metabolic syndrome, fatty liver disease, and bone disorders.
- -
-
Page/Page column 99
(2021/02/19)
-
- SYNTHESIS OF 3-({5-CHLORO-1-[3-(METHYLSULFONYL)PROPYL]-1H-INDOL-2 YL} METHYL)-1-(2,2,2-TRIFLUOROETHYL)-1,3-DIHYDRO-2H-IMIDAZO[4,5-C]PYRIDIN-2-ONE
-
The present invention relates to a chemical synthesis route for preparing the RSV inhibiting compound 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-10 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, and to new compounds used as intermediate compounds in the multistep process.
- -
-
Paragraph 0017
(2021/05/07)
-
- Ex Situ Formation of Methanethiol: Application in the Gold(I)-Promoted Anti-Markovnikov Hydrothiolation of Olefins
-
A protocol for the Au-promoted anti-Markovnikov hydrothiolation of olefins using ex situ generated methanethiol is reported. The use of S-methylisothiourea hemisulfate salt as a solid precursor for methanethiol generation ensures a safe and reliable deliverance of a stoichiometric amount of this thiol. The procedure was shown to work for a broad range of olefins providing the corresponding hydrothiolated adduct in good to excellent yields. Mechanistic evaluations suggest that thiyl radicals are generated and that gold acts as an efficient but stable radical initiator.
- Kristensen, Steffan K.,Laursen, Simon L. R.,Taarning, Esben,Skrydstrup, Troels
-
supporting information
p. 13887 - 13891
(2018/10/02)
-
- 4-diphenylcarboxylic acid compound and preparing method and application thereof
-
The invention relates to a 4-diphenylcarboxylic acid compound and a preparing method and application thereof, and belongs to the field of medicines. The 4-diphenylcarboxylic acid compound is shown inthe formula I. The 4-diphenylcarboxylic acid compound ex
- -
-
Paragraph 0117; 0118; 0019; 0120
(2018/06/21)
-
- GPR40 AGONISTS IN ANTI-DIABETIC DRUG COMBINATIONS
-
Disclosed are compositions comprising (a) a GPR40 agonist and (b) an SGLT2 inhibitor, and methods for treating of disorders that are affected by the modulation of the GPR40 receptor and SGLT2 transporter. Such GPR40 compounds are represented by Formula (I) as follows: wherein ring W, R1, R2, R3, R5, R6, A, and Z, are defined herein.
- -
-
Paragraph 0472
(2017/10/27)
-
- SUBSTITUTED BENZOTHIOPHENYL DERIVATIVES AS GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES
-
Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I) as follows: wherein U1, U2, U3, R1, R2, Z, and W are defined herein.
- -
-
Paragraph 0471
(2017/11/01)
-
- Discovery of methylsulfonyl indazoles as potent and orally active respiratory syncytial Virus(RSV) fusion inhibitors
-
Recently we described a novel class of imidazopyridine compounds that showed exceptional anti-RSV potency in cell culture. However, unfavorable pharmacokinetic (PK) properties and glutathione (GSH) adduct liabilities impeded their further development. In a bid to address the PK and early safety concerns, a small compound library consisting of dozens of scaffold-hopping analogues was designed and synthesized for RSV CPE assay screening, which led to the identification of a new chemical starting point: methylsulfonyl indole compound 8. In this paper, we report the discovery and optimization of a series of methylsulfonyl indazoles as potent RSV fusion inhibitors. In particular, compound 47 was orally efficacious in a RSV mouse model, with 1.6 log unit viral load reduction at 25 mg/kg BID upon oral dosing. The results may have broad implications for the design of new RSV fusion inhibitors, and demonstrate the potential for developing novel therapies for RSV infection.
- Feng, Song,Li, Chao,Chen, Dongdong,Zheng, Xiufang,Yun, Hongying,Gao, Lu,Shen, Hong C.
-
supporting information
p. 1147 - 1157
(2017/08/02)
-
- COMPOSITE PREPARATION, CONTAINING NOVEL 3-(4-(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE AND ANOTHER ACTIVE INGREDIENT, FOR PREVENTING OR TREATING METABOLIC DISEASES
-
The present invention relates to a pharmaceutical composition for preventing or treating metabolic diseases, in which a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative and at least another active ingredient, which is selected from the group consisting of dipeptidyl peptidase-4 (DPPIV) inhibitor-based, sulfonylurea-based, thiazolidinedione (TZD)-based, biguanide-based, and sodium/glucose cotransporter 2 (SGLT2) inhibitor-based drugs, may be administered in combination or in the form of a composite preparation. The use of the composition of the present invention can provide a remarkably excellent blood sugar reducing effect in various animal diabetic disease models, and the composition of the present invention can be favorably used as a pharmaceutical composition for preventing or treating metabolic diseases, such as obesity, diabetes type I, diabetes type II, glucose intolerance symptoms, insulin resistance symptoms, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X.
- -
-
Paragraph 0177-0179
(2017/09/04)
-
- SUBSTITUTED BENZOTHIOPHENYL DERIVATIVES AS GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES
-
Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I) wherein R1, R2, R3, R5, R6, W, and A are defined herein.
- -
-
Page/Page column 96-97
(2016/05/02)
-
- TAK-875 analog, and preparation method and application thereof
-
The invention relates to a TAK-875 analog, and a preparation method and an application thereof, concretely relates to a compound with a structure represented by general formula (I), and various optical isomers, pharmaceutically acceptable salts, solvates
- -
-
Paragraph 0062; 0063
(2016/10/27)
-
- NOVEL 3-(4(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE, METHOD OF PREPARING SAME AND PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING METABOLIC DISEASE INCLUDING SAME AS EFFECTIVE INGREDIENT
-
The present invention relates to a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for the prevention and treatment of metabolic disease. The novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention has excellent activities of activating GPR40 protein and promoting insulin secretion accordingly but has no toxicity when co-administered with other drugs. That is, the novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention can be co-administered with other drugs and can promote the activation of GPR40 protein significantly, so that the composition comprising the same as an active ingredient can be efficiently used as a pharmaceutical composition for the prevention and treatment of metabolic disease such as obesity, type I diabetes, type II diabetes, incompatible glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X, etc.
- -
-
Paragraph 0283-0285
(2016/02/18)
-
- TETRAHYDROPYRIDOPYRIMIDINES AND TETRAHYDROPYRIDOPYRIDINES AS INHIBITORS OF HBSAG (HBV SURFACE ANTIGEN) AND HBV DNA PRODUCTION FOR THE TREATMENT OF HEPATITIS B VIRUS INFECTIONS
-
The present invention provides tetrahydropyridopyrimidines and tetrahydropyridopyridines having the general formula (I) wherein R1, R2, U, W, X, Y and Z are as described herein, as inhibitors of HBsAg (HBV surface antigen) and HBV DNA production for the treatment and prophylaxis of hepatitis B virus infections.
- -
-
Page/Page column 92; 93
(2016/11/21)
-
- PYRROLIDINE GPR40 MODULATORS FOR THE TREATMENT OF DISEASES SUCH AS DIABETES
-
The present invention provides compounds of Formula (I) or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, or a solvate thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.
- -
-
Page/Page column 102
(2015/11/27)
-
- CARBOXYLIC ACID COMPOUNDS IN TREATMENT OF DIABETES MELLITUS
-
The invention relates to compounds for increasing GPR40 recetpor activity and application thereof. These compounds include of a compound of Formula (I), pharmaceutically acceptable salts thereof, solvates thereof, isomers thereof, or produgs of the compou
- -
-
Page/Page column 30
(2015/03/13)
-
- ANTIDIABETIC TRICYCLIC COMPOUNDS
-
Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
- -
-
Page/Page column 74
(2015/04/28)
-
- ANTIDIABETIC TRICYCLIC COMPOUNDS
-
Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
- -
-
Page/Page column 72
(2015/04/28)
-
- Novel dihydroquinolizinones for the treatment and prophylaxis of hepatitis B virus infection
-
The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds.
- -
-
Paragraph 1878; 1879
(2015/08/04)
-
- NOVEL DIHYDROQUINOLIZINONES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
-
The invention provides novel compounds having the general formula (I) wherein R1, R2 R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds in the treatment of the hepatitis B virus.
- -
-
Page/Page column 287
(2015/09/23)
-
- ANTIDIABETIC TRICYCLIC COMPOUNDS
-
Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
- -
-
Page/Page column 94
(2014/02/16)
-
- ANTIDIABETIC TRICYCLIC COMPOUNDS
-
Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
- -
-
Page/Page column 80
(2014/02/16)
-
- Optimization of (2,3-dihydro-1-benzofuran-3-yl)acetic acids: Discovery of a non-free fatty acid-like, highly bioavailable G protein-coupled receptor 40/free fatty acid receptor 1 agonist as a glucose-dependent insulinotropic agent
-
G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) is a free fatty acid (FFA) receptor that mediates FFA-amplified glucose-stimulated insulin secretion in pancreatic β-cells. We previously identified (2,3-dihydro-1-benzofuran-3-yl)acetic acid derivative 2 as a candidate, but it had relatively high lipophilicity. Adding a polar functional group on 2 yielded several compounds with lower lipophilicity and little effect on caspase-3/7 activity at 30 μM (a marker of toxicity in human HepG2 hepatocytes). Three optimized compounds showed promising pharmacokinetic profiles with good in vivo effects. Of these, compound 16 had the lowest lipophilicity. Metabolic analysis of 16 showed a long-acting PK profile due to high resistance to β-oxidation. Oral administration of 16 significantly reduced plasma glucose excursion and increased insulin secretion during an OGTT in type 2 diabetic rats. Compound 16 (TAK-875) is being evaluated in human clinical trials for the treatment of type 2 diabetes.
- Negoro, Nobuyuki,Sasaki, Shinobu,Mikami, Satoshi,Ito, Masahiro,Tsujihata, Yoshiyuki,Ito, Ryo,Suzuki, Masami,Takeuchi, Koji,Suzuki, Nobuhiro,Miyazaki, Junichi,Santou, Takashi,Odani, Tomoyuki,Kanzaki, Naoyuki,Funami, Miyuki,Morohashi, Akio,Nonaka, Masami,Matsunaga, Shinichiro,Yasuma, Tsuneo,Momose, Yu
-
experimental part
p. 3960 - 3974
(2012/07/28)
-
- PRODUCTION METHOD OF OPTICALLY ACTIVE DIHYDROBENZOFURAN DERIVATIVE
-
Provided is a production method of an optically active dihydrobenzofuran derivative. A production method of an optically active form of a compound represented by the formula: wherein each symbol is as defined in the specification, or a salt thereof and the like.
- -
-
Page/Page column 152-153
(2012/09/10)
-
- FUSED CYCLIC COMPOUNDS
-
The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof. The compound or a salt thereof or a prodrug thereof has a GPR40 receptor function modulating action and is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.
- -
-
Page/Page column 79
(2008/06/13)
-
- THERAPEUTIC AGENT FOR DIABETES
-
The present invention provides an agent for the prophylaxis or treatment of diabetes, which is associated with a ferwer side effects such as body weight gain, adipocyte accumulation, cardiac hypertrophy and the like, and which contains a compound represented by the formula: wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.
- -
-
Page/Page column 221
(2008/06/13)
-
- PHARMACEUTICAL COMPOUNDS
-
Fused pyrimidines of formula (I); wherein A represents a thiophene or furan ring; n is 1 or 2; R1 is a group of formula (II); wherein m is 0 or 1; R30 is H or C1-C6 alkyl; R4 and R5 form, together with the N atom to which they are attached, a 5- or 6-membered saturated N-containing heterocyclic group which includes 0 or 1 additional heteroatoms selected from N, S and O, which may be fused to a benzene ring and which is unsubstituted or substituted; or one of R4 and R5 is alkyl and the other is a 5- or 6-membered saturated N-containing heterocyclic group as defined above or an alkyl group which is substituted by a 5- or 6-membered saturated N-containing heterocyclic group as defined above; R2 is selected from formula (a); wherein R6 and R7 form, together with the nitrogen atom to which they are attached, a morpholine, thiomorpholine, piperidine, piperazine, oxazepane or thiazepane group which is unsubstituted or substituted; and formula (b); wherein Y is a C2-C4 alkylene chain which contains, between constituent carbon atoms of the chain and/or at one or both ends of the chain, 1 or 2 heteroatoms selected from O, N and S, and which is unsubstituted or substituted; and R3 is an indazole group which is unsubstituted or substituted; and the pharmaceutically acceptable salt thereof have activity as inhibitors of P13K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with P13 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.
- -
-
Page/Page column 79-80
(2008/06/13)
-
- A facile and efficient synthesis of 14C-labelled sulforaphane
-
Isothiocyanates have gained considerable attention for their role as potent chemopreventive agents. Sulforaphane, 1a (SFN), a naturally occurring isothiocyanate, was isotopically labelled in five steps starting from 3-(methylthio)-1-propanol (2). Reacting 2 with tosyl chloride in the presence of Et3N yielded the tosylate 3. Gently refluxing 3 with K 14CN in DMF gave the nitrile 4b. Reduction to the amine 5b was achieved using BH3-THF. Oxidation with 30% hydrogen peroxide followed by treatment with thiophosgene yielded (±)[1-14C]SFN, 1b. The overall radiochemical yield was 4.4% based on the starting K 14CN. Copyright
- D'Souza, Christopher A.,Amin, Shantu,Desai, Dhimant
-
p. 851 - 859
(2007/10/03)
-
- Substituted anilino-quinazoline (or quinoline) compounds and use thereof
-
The invention concerns amide derivatives of Formula (I), wherein: G is N or CH; R1is a group such as hydroxy, halo, trifluoromethyl, C1-6alkyl and C1-6alkoxy; each of R2and R3is hydrogen, halo, C1-6alkyl, C2-6alkenyl or C2-6alkynyl; R4is a group such as hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy and C3-7cycloalkyl, or R4is of the Formula (IC): —K—J, wherein J is aryl, heteroaryl or heterocyclyl and K is a bond or a group such as oxy and imino, R5is a group such as hydrogen, halo and trifluoromethyl: m is 1-3 and q is 0-4; or pharmaceutically acceptable salts or in vivo cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.
- -
-
-
- Silver Ion Selective Optodes Based on Novel Thia Ether Compounds
-
Flow-through type fiber-optic silver ion selective optodes based on novel cyclic and noncyclic thia crown ether compounds and a lipophilic anionic indicator dye have been developed. Pellicular octadecylsilica beads were coated with a lipophilic organic liquid containing the thia ether compound as the silver ion selective ionophore and LAD-3 as the color changeable indicator dye. The optode system was constructed by packing these color changeable ion sensing beads in a flow-through optical cell (cell volume, 7 μL) having a quartz window attached directly to the distal end of a bifurcated optical fiber. The optode based on a lipophilic thia crown ether that has two sulfur atoms (tetradecyl-14-dithiacrown-4) exhibited the most sensitive response to silver ion of all the optodes investigated. This optode could detect silver ion in concentrations ranging from 10-6 to 10-2 M at pH 7.0 with 0.05 M Tris-H2SO4 buffer as the flowing solution by measuring the absorbance change in the sensing beads at 516 nm. This optode showed a highly selective response to Ag+ without any interference from other transition metal ions, except for Hg2+, up to 10-3 M, as well as alkali metal and alkaline earth metal ions up to 1 M. Optodes employing highly lipophilic ionophores showed good reproducible response to Ag+ for at least 2 weeks.
- Hisamoto, Hideaki,Nakagawa, Eriko,Nagatsuka, Kazuhisa,Abe, Yoko,Sato, Sayaka,Siswanta, Dwi,Suzuki, Koji
-
p. 1315 - 1321
(2007/10/02)
-
