cas 122320-73-4, Rosiglitazone | Articles data

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Synthetic optimization of rosiglitazone and related intermediates for industrial purposes
As an important newly Food and Drug Administration (FDA)-approved drug for treating diabetes, rosiglitazone (1) has received much attention from researchers in many areas. To search for an economical and convenient synthesis method for 1, we explored the reaction conditions and workup of a scalable five-step synthetic route by an orthogonal method to determine the best condition for each reaction step. The starting materials are commercially available, including 2-chloropyridine (2), N-methylethanolamine (3), 4-fluorobenzaldehyde (4a) or 4-hydroxybenzaldehyde (4b), and 1,3-thiazolidine-2,4-dione (5). The five sequential reaction steps are cyclization, alkylation, etherification, condensation, and reduction, having optimal yield of 90, 99, 59, 75, and 91 %, respectively. The best overall yield to synthesize rosiglitazone based on compound 2 was 40 %, being suitable for industrial purposes, using water as a green solvent and avoiding column chromatography during the last three reaction steps.
Meng, Ge,Zheng, Meilin,Dong, Mengshu,Gao, Yang,Zheng, Aqun,Li, Zhenyu,Hu, Ruizhi
p. 2023 - 2033
(2016)
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Microwave-assisted synthesis of the antihyperglycemic drug rosiglitazone
We developed a simple, rapid, high yielding, and environmentally benign microwave assisted total synthesis of rosiglitazone, an antihyperglycemic agent for diabetes mellitus Type II. We used microwave heating successfully to improve reactions in four of six steps and obtain quicker and higher yields. In addition, all intermediates were isolated in good yields with crystallizations only and did not require chromatographic separations.
Gaonkar, Santosh L.,Shimizu, Hiroki
p. 3314 - 3317
(2010)
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Preparation method of rosiglitazone
The invention provides a preparation method of rosiglitazone. The preparation method is characterized by comprising the following steps: reacting 2-chloropyridine with 2-methylaminoethanol under the catalysis of sodium triphenylmethyl to generate 2-[N-methyl-N-(2-pyridine) amino] ethanol; then carrying out Williamson synthesis reaction on the 2-[N-methyl-N-(2-pyridine) amino] ethanol and 4-fluorobenzaldehyde under the catalysis of bis (trimethylsilyl) amino potassium to obtain 4-[2-[N-methyl-N-(2-pyridine) amino] ethoxy] benzaldehyde; then carrying out condensation reaction with thiazoline-2,4-diketone to obtain 5-{4-[2-[N-methyl-N-(2-pyridine) amino] ethoxy] benzylidene} thiazoline-2, 4-diketone; and carrying out reduction reaction under the catalysis of an organic manganese reagent to obtain the rosiglitazone. The preparation method is simple, mild in condition, high in reaction yield and suitable for industrial production.
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(2020/12/29)

Organocatalytic Cyclization of COS and Propargylic Derivatives to Value-Added Heterocyclic Compounds
The organocatalytic cyclization of propargylic amines/amides with carbonyl sulfide (COS) was firstly achieved by employing COS adducts of Lewis base (LB) as organocatalysts, affording various functionalized 1,3-thiazolidine-2-ones, and 1,3-thiazolidine-2,4-diones derivatives in a highly chemo- and stereoselective manner. The isotope labeling and stoichiometric experiments suggested the LB-COS adducts preferentially mediated basic ionic pair mechanism. Furthermore, the practical application of this methodology was highlighted by the highly efficient synthesis of rosiglitazone using COS as sulfur source.
Zhou, Hui,Zhang, Rui,Mu, Sen,Zhang, Hui,Lu, Xiao-Bing
p. 5728 - 5732
(2019/06/04)

Robust Acenaphthoimidazolylidene Palladacycles: Highly Efficient Catalysts for the Amination of N-Heteroaryl Chlorides
A series of robust N-heterocyclic carbene palladacycles have been successfully developed. These showed high catalytic activity and selectivity toward the challenging amination of N-heteroaryl chlorides. Different primary and secondary amines were fully compatible with this catalytic system. Remarkably, no double amination products could be detected when primary amines were utilized in our catalytic transformation. Furthermore, the protocol has been successfully extended to synthesize rosiglitazone, a clinical drug for diabetes mellitus, highlighting its potential pharmaceutical feasibility.
Deng, Qinyue,Zhang, Yang,Zhu, Haibo,Tu, Tao
supporting information
p. 2364 - 2368
(2017/09/06)

An alternative synthetic route for an antidiabetic drug, rosiglitazone
A convenient and scalable four-step novel route has been developed for the synthesis of rosiglitazone (8), an antidiabetic drug. This multistep route requires 4-fluoro benzaldehyde (4), 2,4-thiazolidinedione (6) and 2-chloro pyridine (1) as key reactants and gives overall better yield of rosiglitazone. In addition, some steps have been accelerated, which leads to an overall time saving of 10 h.
Jawale, Dhanaji V.,Pratap, Umesh R.,Mane, Ramrao A.
p. 924 - 928
(2012/03/26)

A METHOD FOR PREPARATION OF THIAZOLIDINEDIONE DERIVATIVES
The present invention offers the conjugate reduction of α-β-unsaturated thiazolidinedione derivatives which involves the reagents cobalt ion in the form of cobaltous chloride hexahydrate, the ligand dimethyl glyoxime in N, N dimethyl formamide, the reducing agent sodium borohydride and the solvent media for the reaction is polyethylene glycol (PEG).
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Page/Page column 6-7

(2009/10/18)

Process for the Preparation of Intermediates of Rosiglitazone, Rosiglitazone and New Polymorphic Forms Thereof
The invention relates to a polymorphic form of 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene)-2,4-thiazolidinedione (Formula (I)): to a process for its preparation and to the use of such compound for preparing rosiglitazone in the form of a free base or a salt thereof. The invention also relates to a polymorphic form of rosiglitazone in the form of a free base, to a process for its preparation and to the use of such polymorph for preparing a salt of rosiglitazone. The invention also relates to a process of preparing a polymorphic form of a rosiglitazone salt.
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Page/Page column 5

(2009/09/28)

An improved process for hydrogenation of 5-(substituted Benzylidene) 2,4- Thiazolidine Dione compounds to give corresponding ( +/- ) 5- (substituted Benzyl ) 2,4-Thiazolidine Dione
The present provides a preparation of (+/-) -5- [substituted. phenyl methyl ] - 2,4-thiazolidinediones from 5-[ substituted benzylidene ]-2,4-thiazolidinediones by catalytic hydrogenation using precious metal catalyst, using DMF or formic acid [ or aqueous formic acid] and perchloric acid.
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Page/Page column 6

(2008/06/13)

PROCESS FOR THE SYNTHESIS OF BENZYLIDENE ROSIGLITAZONE BASE
Process for the synthesis of 5-{4-[N-methyl-N- (2-pyridyl)-amino-ethoxy]- 5 benzylidene}-thiazolidine-2, 4-dione (INN name: benzylidene-rosiglitazone) of formula (I), which consist of the following steps: (I) Step a) reaction of 2-chloro-pyridine and 2-(N-methylamino)-ethanol Step b) reaction of the obtained compound of formula (III) with 4- 0 fluorobenzaldehyde Step c) reaction of the obtained compound of formula (IV) with thiazolidine-2, 4-dione. (III), ((IV). characterized by - dissolving 4-{2-[N-methyl-N- (2-pyridyl) amino]-ethanol of formula (III) obtained in Step a) in toluene and using it in Step b) without isolation; - reacting the solution of compound of formula (III) in toluene in Step b) with 4-fluorobenzaldehyde in the presence of aqueous alkali hydroxide solution and phase transfer catalyst at 25-50 °C; - reacting the solution of the benzaldehyde derivative of formula (IV) obtained in Step b) in toluene in Step c) and isolating the desired product.
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Page/Page column 9

(2008/06/13)

A PROCESS FOR THE PREPARATION OF SUBSTITUTED PHENYL ETHER COMPOUNDS AND ROSIGLITAZONE
A novel process for the preparation of a compound of the formula (II), which is useful as intermediate compound for the preparation of thiazolidinedione derivatives, such as rosiglitazone, pioglitazone, troglitazone and ciglitazone, is disclosed. The novel process comprising reacting a compound of the formula (III) with a compound of the formula (IV) in a mixture of a non-polar water immiscible organic solvent and water (two phase system) with an alkali metal hydroxide or an alkali metal carbonate as a base in the presence of a phase transfer catalyst. In the first aspect of the present invention comprising reacting 2-(N-methyl-N-(2- pyridyl) ethanol with 4-fluorobenzaldehyde in the mixture of a non-polar water immiscible organic solvent, preferably toluene, and water with an alkali metal hydroxide or an alkali metal carbonate as a base, preferably potassium hydroxide, in the presence of a phase transfer catalyst, e.g. tetra n-butylammonium hydrogensulphate or benzyltriethylammonium chloride, to obtain 4-[2-(N-methyl-N-(2- pyridyl)amino)ethoxy]benzaldehyde, which is the key intermediate for preparing rosiglitazone and its salts, e.g. maleate salt or phosphate salt, useful in the treatment of Type II diabetes.
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Page/Page column 14

(2008/06/13)

Stabilized pharmaceutical composition comprising antidiabetic agent
This invention discloses a stabilized pharmaceutical composition comprising an antidiabetic agent and a stabilizer. The preferred stabilizers are selected from the group consisting of ascorbic acid, malic acid, maleic acid, tartaric acid, furmaric acid, citric acid, or combinations thereof. The antidiabetic agent is selected from the group consisting of [(±)5-[[2-(5-ethyl-2-pyridinyl)ethoxyl]phenyl]methyl]-thiazolidine-2,4-dione and (±)5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione. This invention also discloses amorphous forms of said antidiabetic agents and a process of preparation thereof, and a method for medical treatment of diabetic mellitus using said pharmaceutical composition.
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Page/Page column 12

(2008/06/13)

METHOD FOR THE PREPARATION OF ROSIGLITAZONE
Preparation of rosiglitazone of formula (I) by reduction of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]-benzylidene]thiazolidine-2,4-dione of formula (II) using a mixture of formic acid of formula (III) and a basic amine of formula (IV), or the ammonium salt of formic acid of formula (V), wherein R1, R2, and R3 stand for hydrogen or an alkyl group (C1-C5), under the catalysis of a transition metal.
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Page/Page column 5

(2008/06/13)

A PROCESS FOR THE CRYSTALLIZATION OF ROSIGLITAZONE AND ITS DERIVATIVES FROM MIXED SOLVENTS
Crystallization of rosiglitazone of formula (I), its penultimate of formula (II), or salts with acids of formula (III), wherein HX stands for a mineral or carboxylic acid, is carried out from mixed organic solvents, consisting of mixtures of carboxylic acids, particularly formic acid, acetic acid or propionic acid, with aliphatic alcohols, particularly methanol, ethanol, 1-propanol, 2- propanol, butanols or amyl alcohols.
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Page/Page column 10-16

(2008/06/13)

METHOD FOR THE PREPARATION OF ROSIGLITAZONE
A method for the preparation of rosiglitazone of formula (I) by reduction of 5-[4-[2-(N-methyl- N-(2-ρyridyl)amino)ethoxy]-benzylidene]thiazolidine-2,4-dione of formula (II), the reduction being carried out using at least one borohydride of general formula MBH4, wherein M stands for a cation from the group of Na, Li, K, Zn and R4N, and R stands for a C1-C5 alkyl group, under the catalysis of cobalt salts in the presence of at least one complexing agent and a suitable solvent.
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Page/Page column title page; 3; 7; 9

(2008/06/13)

USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS
The present invention relates to the use of a substituted 2-phenylbenzimidazole of formula I wherein R1, R2, R3, R 4, R5 and m have the meanings given in the claims, for the preparation of a medicament for the treatment or prevention of diseases involving glucagon receptors, as well as new compounds of formula I wherein R1 is a group of formula
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(2008/06/13)

Process for the preparation of 5-[4-[2-[N-methyl-N-(2-pyridyl) amino] ethoxy] phenyl methyl] thiazolidine-2, 4-dione maleate
The present invention discloses a process for the preparation of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]phenyl methyl]thiazolidine-2,4-dione maleate (VI) comprising the steps of Coupling 2-[N-methyl-N-(2-pyridyl)amino]ethanol (I) and 4-fluorobenzaldehyde (II) in N,N-dimethylformamide, isolating the coupled product 4[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzaldehyde (III), converting said isolated benzaldehyde compound (III) to 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene]thiazolidine-2,4-dione (IV) and purifying the same, reducing 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene]thiazolidine-2,4-dione, by a novel reduction method for making 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]phenyl methyl]thiazolidine-2,4-dione (V). This reduction method involves reacting the compound (IV) with a novel metal legand complex and a reducing agent, purifying the product (V) obtained by a new method reported in the present invention and converting the said thiazolidine-2,4-dione compound (V) into a pharmaceutically acceptable salt.
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(2008/06/13)

A PROCESS FOR PURIFICATION
The present invention provides a process for purification of pharmaceutically active compounds selected from the group consisting of thiazolidinedione derivatives and trans-3-Ethyl-2,5-dihydro-4-methyl-N- [2-[4-[[[[(4-methylcyclohexyl)amino] carbonyl] amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide comprising extraction in a solvent comprising an alkanol (C1-C4) and ammonia.
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Page/Page column 13

(2010/02/12)

INDENE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF
The inventive indene derivatives of formula (I) are capable of selectively modulating the activities of peroxisome proliferator activated receptors (PPARs), causing no adverse side effects, and thus, they are useful for the treatment and prevention of disorders modulated by PPARs, i.e., metabolic syndromes such as diabetes, obesity, arteriosclerosis, hyperlipidemia, hyperinsulinism and hypertension, inflammatory diseases such as osteoporosis, liver cirrhosis and asthma, and cancer.
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Page/Page column 67

(2010/02/14)

SYNTHESIS OF ANTIDIABETIC ROSIGLITAZONE DERIVATIVES
A process of preparing rosiglitazone, or a pharmaceutically acceptable salt thereof, which process employs an intermediate metabisulphite complex of 4-[2-(N-methyl-N-(2-pyridyl)amino) ethoxy] benzaldehyde, which metabisulphite complex is represented by following formula (III); where X represents an alkali metal. The present invention further provides rosiglitazone, or a pharmaceutically acceptable salt thereof, prepared by the above process.
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Page/Page column 16

(2008/06/13)

PROCESS FOR THE PREPARATION OF ROSIGLITAZONE
The present invention relates to a process for the preparation of 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl-2,4-thiazolidinedione of formula (I) (Rosiglitazone), which comprises the reaction of 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxyl]benzylidene-2,4-thiazolidinedione of formula (II), with a 1,4-dihydropyridine of general formula (III).
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Page/Page column 10 - 11

(2008/06/13)

PROCESS
The present invention relates to processes for the preparation of rosiglitazone, rosiglitazone prepared thereby and pharmaceutical compositions and therapeutic uses thereof, and methods of treatment employing the same.
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Page/Page column 14-15

(2008/06/13)

PROCESS FOR PREPARING THIAZOLIDINEDIONES
This invention provides a process for reducing an exocyclic double bond at the 5-position of a thiazolidinedione moiety of a thiazolidinedione precursor comprising the steps of: a) preparing a solution or suspension of the thiazolidinedione precursor in a non-ether solvent medium with a base, and b) combining the solution or suspension with a dithionite source. Preferred solvent media include aqueous N,N-dimethylformamide. Sodium dithionite is a preferred dithionite source. In particular the application discloses preparation processes for Pioglitazone, Rosilitazone and Troglitazone.
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Page/Page column 15-16

(2008/06/13)

Agent for improving ketosis
An agent for improving ketosis which comprises an insulin sensitizer, which has an excellent action and low toxicity.
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(2008/06/13)

Drug comprising combination
A TNF-α inhibitor comprising an insulin sensitizer in combination with an HMG-CoA reductase inhibitor is useful as an agent for the prophylaxis or treatment of an inflammatory disease and the like.
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(2008/06/13)

Neovascularization inhibitors
An angiogenesis inhibitor containing a compound represented by the formula wherein R4 is an optionally substituted hydrocarbon group and the like; Xa is a bond and the like; k is an integer of 1 to 3; Ya is an oxygen atom and the like; ring Ea is a benzene ring optionally having additional substituent(s); p is an integer of 1 to 8; R5 is a hydrogen atom and the like; q is an integer of 0 to 6; r is 0 or 1; R8 is a hydroxy group and the like; and R6 and R7 are hydrogen atoms and the like, or a salt thereof is useful as an agent for the prophylaxis or treatment of tumor and the like.
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(2008/06/13)

Combinations comprising dipeptidylpeptidase-iv inhibitor
The invention relates to a combination which comprises a DPP-IV inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6-phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers, α-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and α2-adrenergic antagonists, for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more especially type 2 diabetes mellitus, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; and the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight.
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(2008/06/13)

Use of thiazolidinediones for the treatment of atherosclerosis and eating disorders
The use of a compound of formula (I): or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof and/or a pharmaceutically acceptable solvate thereof, wherein:A1 represents a substituted or unsubstituted aromatic heterocyclyl group;R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group;R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond;A2 represents a benzene ring having in total up to five substituents; andn represents an integer in the range of from 2 to 6, for the manufacture of a medicament for use in the treatment and/or prophylaxis of atherosclerosis and/or for the regulation of appetite and food intake.
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(2008/06/13)

CHEMICAL COMPOUNDS
A compound of formula (I) or a pharmaceutically acceptable salt, solvate, or hydrolysable ester thereof, .Wherein:R1 and R2 are independently hydrogen or C1-3 alkyl;X represents a bond, CH2 or O;R3 and R4 are independently hydrogen, C1-6 alkyl, OCH3, CF3, allyl or halogen;X1 is CH2, SO2, or CO;R5 is -C1-6 alkyl (optionally substituted by C1-6alkoxy or C1-6alkylthio), -C2-6 alkenyl, -C0-6 alkyl phenyl (wherein the phenyl is optionally substituted by one or more CF3, halogen, C1-3 alkyl, C1-3 alkoxy), -COC1-6 alkyl, SO2C1-6 alkyl ;R6 is phenyl or a 6 membered heteroaryl group containing 1,2 or 3 N atoms wherein the phenyl or heteroaryl group is optionally substituted with 1, 2 or 3 moieties selected from the group consisting of C1-6 alkyl, halogen, -OC1-6 alkyl, -SO2C1-3 alkyl, phenyl (optionally substituted by one or more groups selected from halogen, CF3, C1-3 alkyl, OC1-3 alkyl, acetyl, CN).
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Page 91

(2010/02/05)

Polymer-assisted solution phase synthesis of the antihyperglycemic agent Rosiglitazone (Avandia).
The commercially important antihyperglycemic agent Rosiglitazone 1(Avandia) has been prepared in high purity by a multi-step, polymer-assisted solution phase (PASP) synthesis without the need for the conventional chromatographic purification of any intermediates.
Li, Xin,Abell, Chris,Warrington, Brian H,Ladlow, Mark
p. 4392 - 4395
(2007/10/03)

Process for the preparation of substituted thiazolidinedione
A process for preparing a compound of formula (I, I) or a tautomeric form thereof or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, wherein: J represents O or S; T represents a substituted or unsubstituted aryl group and T1 is O or S; which process comprises reducing a compound of formula (II, II) or a tautomeric form thereof or a salt thereof or a solvate thereof, wherein T and T1 are as defined in relation to formula (I), with a complex hydride reducing agent or a source of a complex hydride reducing agent; and thereafter, as required, preparing a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate of the compound of formula (I) or a tautomeric form thereof.
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(2008/06/13)

Process for the preparation of thiazolidinedione derivatives
A process for preparing a compound of formula (I): or a tautomeric form thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein:A1 represents a substituted or unsubstituted aromatic heterocyclyl group;R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group;A2 represents a benzene ring having in total up to five substituents; andn represents an integer in the range of from 2 to 6, which process comprises catalytically reducing a compound of formula (II): wherein A1, R1, A2 and n are as defined in relation to formula (I), characterised in that the reduction reaction is carried out using a hydrogen pressure above 20psi; and thereafter if required forming a pharmaceutically acceptable salt and/or a pharmaceutically acceptable solvate of the compound of formula (I).
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Page 5

(2008/06/13)

METHOD OF INHIBITING ANGIOGENESIS
Angiogenesis is inhibited and the growth of tumors is treated by administering an effective amount of a PPAR gamma ligand/agonist, optionally with an RXR receptor ligand.
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(2008/06/13)

Use of thiazolidinedione derivatives in the treatment of insulin resistance
The present invention provides methods of using thiazolidinedione in the treatment of insulin resistance.
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(2008/06/13)

Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus
Novel methods of using thiazolidinone derivatives and related antihyperglycemic agents to treat populations at risk for developing noninsulin-dependent diabetes mellitus (NIDDM) and complications arising therefrom are disclosed. In one embodiment, the compounds of the invention are used to treat polycystic ovary syndrome in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus. In another embodiment, the compounds of the invention are used to treat gestational diabetes in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus.
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(2008/06/13)

Method for preventing and for treating autoimmune disease
A method for preventing or treating autoimmune diseases (excluding type I diabetes) by administering an insulin resistance improving substance as an active ingredient.
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(2008/06/13)

Regiospecific reduction of 5-benzylidene-2,4-thiazolidinediones and 4- oxo-2-thiazolidinethiones using lithium borohydride in pyridine and tetrahydrofuran
The novel regiospecific and general reduction of 5-benzylidene-2,4- thiazolidinediones and 5-benzylidene-4-oxo-2-thiazolidinethiones to the corresponding 5-benzyl derivatives has been accomplished using lithium borohydride in pyridine and tetrahydrofuran. Sodium borohydride and lithium chloride can also be used under these conditions, which represents a cheaper alternative to lithium borohydride. (C) 2000 Elsevier Science Ltd.
Giles, Robert G.,Lewis, Norman J.,Quick, John K.,Sasse, Michael J.,Urquhart, Michael W. J.,Youssef, Latifa
p. 4531 - 4537
(2007/10/03)

Solid-phase synthesis of BRL 49653
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Brummond, Kay M.,Lu, Jianliang
p. 1723 - 1726
(2007/10/03)

Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of insulin resistant subjects with normal glucose tolerance in order to prevent or delay the onset of noninsulin-dependent mellitus
Novel methods of using thiazolidinone derivatives and related antihyperglycemic agents to treat populations exhibiting insulin resistent non-impaired glucose tolerance (IRNIGT) in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus (NIDDM) and complications arising therefrom are disclosed.
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(2008/06/13)

Use of troglitazone and related compounds for the treatment of the climacteric symptoms
The present invention is directed toward the use of the drug Troglitazone and related thiazolidinedione compounds in the treatment of the climacteric and cancer. This use is based on the novel discovery that Troglitazone inhibits steroidogenesis in granulosa cell cultures. This activity is believed to result from the ability of thiazolidinedione derivatives to act as a ligand for the orphan steroid receptor peroxisome proliferator-activated receptor gamma (PPARγ). Troglitazone and related compounds can therefore be used to prevent excessive uterine bleeding during. Further, enhanced translocation of this orphan nuclear receptor into the nucleus of cells will block transcription in rapidly proliferating cancer cells that express PPARγ, resulting in loss of cell viability.
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(2008/06/13)

Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus
Novel methods of using thiazolidinone derivatives and related antihyperglycemic agents to treat populations experiencing impaired glucose intolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus (NIDDM) and complications arising therefrom are disclosed.
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(2008/06/13)

Facile Biocatalytic Reduction of the Carbon-Carbon Double Bond of 5-Benzylidenethiazolidine-2,4-diones. Synthesis of (+/-)-5-(4-ethoxy>benzyl)thiazolidine-2,4-dione (BRL 49653), its (R)-(+)-Enantiomer and Analogues
A novel biotransformation system for the reduction of carbon-carbon double bonds in 5-benzylidenethiazolidine-2,4-diones, to give the corresponding 5-benzylthiazolidine-2,4-diones, using whole cells of red yeasts is described.These reduced compounds, which are recovered in good yield, are of potential use in the treatment of non-insulin dependent diabetes mellitus.The mild reaction conditions developed allow reduction of 5-benzylidenethiazolidine-2,4-diones containing other functionalities which are not compatible with alternative reduction methods.The biocatalytic reduction is enantioselective and the synthesis of R-(+)-5-(4-ethoxy>benzyl)thiazolidine-2,4-dione by Rhodotorula rubra CBS 6469 and structure confirmation by X-ray crystallography is detailed.Optimisation of reaction conditions (including immobilisation) for these whole cell reduction systems is described.
Cantello, Barrie C. C.,Eggleston, Drake S.,Haigh, David,Haltiwanger, R. Curtis,Heath, Catherine M.,et al.
p. 3319 - 3324
(2007/10/02)

benzyl>-2,4-thiazolidinediones as Potent Antihyperglycemic Agents
A series of -2,4-thiazolidinediones and benzyl>-2,4-thiazolidinediones was synthesized from the corresponding aldehydes.Compounds from the urea series, exemplified by 16, showed antihyperglycemic potency comparable with known agents of the type such as pioglitazone and troglitazone (CS-045).The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies.Evaluation of antihyperglycemic activity together with effects on blood hemoglobin content, to determine the therapeutic index, was performed in 8-day repeat administration studies in genetically obese C57 BI/6 ob/ob mice.From these studies, BRL 49653 (37) has been selected, on the basis of antihyperglycemic potency combined with enhanced selectivity against reductions in blood hemoglobin content, for further evaluation.
Cantello, Barrie C.C.,Cawthorne, Michael A.,Cottam, Graham P.,Duff, Peter T.,Haigh, David,et al.
p. 3977 - 3985
(2007/10/02)

Compounds
Compounds of formula (I): STR1 or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine.
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(2008/06/13)

Compounds
Compounds of formula (I): STR1 or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine.
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(2008/06/13)

COMPOUNDS
Compounds of formula (I) or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine
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(2008/06/13)