- Synthesis of new troglitazone derivatives: Anti-proliferative activity in breast cancer cell lines and preliminary toxicological study
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Breast cancer is the most prevalent cancer in women. The development of resistances to therapeutic agents and the absence of targeted therapy for triple negative breast cancer motivate the search for alternative treatments. With this aim in mind, we synth
- Salamone, Stéphane,Colin, Christelle,Grillier-Vuissoz, Isabelle,Kuntz, Sandra,Mazerbourg, Sabine,Flament, Stéphane,Martin, Hélne,Richert, Lysiane,Chapleur, Yves,Boisbrun, Michel
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p. 206 - 215
(2012/07/14)
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- Methods for predicting the response to statins
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The invention provides methods for optimizing therapeutic efficacy for treating hypercholesterolemia in a subject having a cardiovascular disease (CVD), comprising (a) determining subject characteristics that affect the likelihood of reaching a goal level of low density lipoprotein (LDL); and (b) obtaining success probabilities of a variety of statin treatments for reaching said goal level of LDL using said subject characteristics and a multivariate model; and (c) administrating the optimal statin treatment with the highest success probability of step (b) to said subject thereby optimizing therapeutic efficacy for treating hypercholesterolemia in said subject.
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- USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS
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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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- Agent for improving ketosis
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An agent for improving ketosis which comprises an insulin sensitizer, which has an excellent action and low toxicity.
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- Structure-activity requirements for the antiproliferative effect of troglitazone derivatives mediated by depletion of intracellular calcium
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Depletion of calcium from the endoplasmic reticulum has shown to affect protein synthesis and cell proliferation. The anticancer effect of troglitazone was reported to be mediated by depletion of intracellular calcium stores resulting in inhibition of translation initiation. The unsaturated form of troglitazone displays similar anticancer properties in vitro. In this letter, we report our findings on the minimum structural requirements for both compounds to retain their calcium release and antiproliferative activities.
- Fan, Yun-Hua,Chen, Han,Natarajan, Amarnath,Guo, Yuhong,Harbinski, Fred,Iyasere, Julia,Christ, William,Aktas, Huseyin,Halperin, Jose A.
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p. 2547 - 2550
(2007/10/03)
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- Drug comprising combination
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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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- Neovascularization inhibitors
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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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- Combinations comprising dipeptidylpeptidase-iv inhibitor
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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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- 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
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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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- Use of thiazolidinedione derivatives in the treatment of insulin resistance
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The present invention provides methods of using thiazolidinedione in the treatment of insulin resistance.
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- Method for preventing and for treating autoimmune disease
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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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- Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives
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Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1,3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPARγ have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.
- Reddy, K. Anji,Lohray,Bhushan,Reddy, A. Sekar,Mamidi, N. V. S. Rao,Reddy, P. Papi,Saibaba,Reddy, N. Jaipal,Suryaprakash,Misra, Parimal,Vikramadithyan, Reeba K.,Rajagopalan
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p. 3265 - 3278
(2007/10/03)
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- Use of thiazolidinediones to ameliorate the adverse consequences of myocardial ischemia on myocardial function and metabolism
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The present invention provides methods and compositions for (a) enhancing resistance to myocardial ischemia associated dysfunction, including contraction (systolic), relaxation (diastolic) and metabolic dysfunction, comprising the step of administering to a human determined to be susceptible to myocardial ischemia an effective amount of an insulin sensitizer; and (b) reducing hypertension comprising the step of administering to a hypertensive human determined to have normal insulin sensitivity, an effective amount of an insulin sensitizer. In a particular embodiment, the sensitizer comprises a thiazolidinedione compound, such as triglitazone.
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- 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
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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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- Treatment and prophylaxis of pancreatitis
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Insulin sensitizers, especially thiazolidinedione compounds, such as troglitazone, are useful for the treatment and prevention of pancreatitis.
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- Treatment and prophylaxis of osteoporosis
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Compounds of formula (I): STR1 where R1, R2, R4 and R5 are hydrogen or alkyl and R3 is hydrogen, alkyl or various organic groups are effective against osteoporosis at doses at which they also effectively control diabetes.
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- Thiazolidine derivatives for the treatment of psoriasis
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A new medical use for certain thiazolidine derivatives is disclosed. Specifically, treatment of hyperproliferative epithelial cell conditions, such as psoriasis, by administration of thiazolidinediones or 5'-aryl substituted thiazolidine derivatives is described. Appropriate chemical structures, synthetic reactions, formulations, routes of administration and dosages are included.
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- Thiazolidine derivatives having anti-hypertensive activity and their therapeutic use
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Thiazolidine derivatives of formula (I): STR1 (in which: R1, R2, R4, R5 are each hydrogen or alkyl; and R3 is hydrogen, aliphatic acyl, alkoxy-carbonyl, or arylcarbonyl and pharmaceutically acceptable salts thereof are anti-hypertensive agents and are useful in the treatment of obesity-related hypertension.
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- Disposition and metabolism of the new oral antidiabetic drug troglitazone in rats, mice and dogs
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The pharmacokinetics of troglitazone (CAS 97322-87-7, CS-045), a new oral antidiabetic drug for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), were investigated in rats, mice and dogs following oral and intravenous administration of 14C-labeled troglitazone at doses of 5 mg/kg. The absorption rates, calculated from the AUC ratios of total radioactivity after oral and intravenous administration, or from the biliary excretion rate after intraduodenal administration in rats were both as high as 75%. High uptake by the liver, one of the pharmacological target organs, was demonstrated in both rats and mice. Furthermore, in the KK mouse, an obese NIDDM model animal, the radioactivity was incorporated selectively as troglitazone itself to muscle, the peripheral target organ. Troglitazone reversibly bound to serum albumin with a high ratio (> 99%). Troglitazone was mostly metabolized to the conjugates: sulfate (M 1) and glucuronide (M 2). The oxidized metabolite, a quinone-type metabolite (M 3), was found to be further metabolized to the sulfate (U 2). The biliary excretion rates of these conjugates were high in each animal, and the occurrence of enterohepatic circulation of the conjugates was also suggested. Sex differences in pharmacokinetics were observed in rats; i.e. females showed a higher plasma concentration of troglitazone, and a lower concentration of M 1, than males, and they excreted the sex-related metabolite, a hydroxylated M 1 (U 1), in the bile.
- Kawai, Kenji,Kawasaki-Tokui, Yoko,Odaka, Tomoyo,Tsuruta, Fujiko,Kazui, Miho,Iwabuchi, Haruo,Nakamura, Takemichi,Kinoshita, Takeshi,Ikeda, Toshihiko,Yoshioka, Takao,Komai, Toru,Nakamura, Kan-Ichi
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p. 356 - 368
(2007/10/03)
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- Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of disease states at risk for progressing to noninsulin-dependent diabetes mellitus
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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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- 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
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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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- Benzylidenethiazolidine derivatives and their use for the inhibition lipid peroxides
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Benzylidenethiazolidine compounds of formula (I): STR1 [in which R1, R2 and R5 are each hydrogen or alkyl; R3 and R4 are each hydrogen, alkyl, formyl, alkylcarbonyl, arylcarbonyl, carboxy, alkoxycarbo
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- THIAZOLIDINE DERIVATIVES, THEIR PREPARATION AND USE
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Compounds of formula (I): (in which R1-R7 are hydrogen or various organic groups, n is 1-10, Ar is an aromatic group, U is CH2 or a carbon atom doubly bonded to either one of its adjacent carbons, and W is >CH2, >C=0 , >CHOH, >C=NOH or various derivatives thereof) have the ability to lower the levels of blood lipid peroxides and blood sugars and to inhibit the activity of aldose reductase; they may be used therapeutically for these purposes.
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- Thiazolidine derivatives for the treatment of hypertension
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This invention relates to a second medical use of thiazolidine compounds having anti-diabetic properties. These compounds are also of use for the control of essential hypertension.
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- Studies on hindered phenols and analogues. 1. Hypolipidemic and hypoglycemic agents with ability to inhibit lipid peroxidation
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A series of hindered phenols were investigated as hypolipidemic and/or hypoglycemic agents with ability to inhibit lipid peroxidation. 1,3-Benzoxathioles (9 and 22), phenoxypentanoic acid (34), phenoxypentanol (35a), phenoxynonanol (35b), phenylchloropropionic acid having a chromanyl group (25), and a thiazolidine compound (27) derived from 25, all having a hindered phenol group, were prepared and examined. Compound 27 showed the expected biological properties in vivo and in vitro without any liver weight increase. Biological activities of the analogous thiazolidine compounds, 43-58, were compared. Thus, roxy-2,5,7,8-tetramethylchroman-2-yl(methoxy]-benzyl]-2,4-thiazolidinedione (27) (CS-045) was found to have all our expected properties and was selected as a candidate for further development as a hypoglycemic and hypolipidemic agent.
- Yoshioka,Fujita,Kanai,Aizawa,Kurumada,Hasegawa,Horikoshi
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p. 421 - 428
(2007/10/02)
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- Thiazolidine derivatives, their preparation and compositions containing them
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The compounds of formula (I): STR1 [in which: R1 and R2 are the same or different and each represents hydrogen or C1 -C5 alkyl; R3 represents hydrogen, an acyl group, a (C1 -C6 alkoxy)carbonyl group or an aralkyloxycarbonyl group; R4 and R5 are the same or different and each represents hydrogen, C1 -C5 alkyl or C1 -C5 alkoxy, or R4 and R5 together represent a C1 14 C4 alkylenedioxy group; n is 1, 2 or 3; W represents the --CH2 --, >CO or >CH--OR6 group (in which R6 represents any one of the atoms or groups defined for R3 and may be the same as or different from R3); and Y and Z are the same or different and each represents oxygen or imino] and pharmaceutically acceptable salts thereof have various valuable therapeutic effects on the blood system and may be prepared by a process which includes reacting a corresponding halopropionic acid derivative with thiourea.
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