WO2009090210A2 - Combination of metformin and an mtp inhibitor - Google Patents
Combination of metformin and an mtp inhibitor Download PDFInfo
- Publication number
- WO2009090210A2 WO2009090210A2 PCT/EP2009/050418 EP2009050418W WO2009090210A2 WO 2009090210 A2 WO2009090210 A2 WO 2009090210A2 EP 2009050418 W EP2009050418 W EP 2009050418W WO 2009090210 A2 WO2009090210 A2 WO 2009090210A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- phenyl
- metformin
- treatment
- piperidin
- biphenyl
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a combination of the anti-diabetic drug metformin and the MTP (microsomal triglyceride transfer protein) inhibitor (+)-phenyl- (4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester and the use thereof for combined administration in the treatment or prevention of diabetes mellitus type 2 conditions.
- MTP microsomal triglyceride transfer protein
- the invention further relates to products containing as first active ingredient metformin and as second active ingredient the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)- amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester, as combined preparations for simultaneous or sequential use in the treatment or prevention of diabetes mellitus type 2; and to related pharmaceutical compositions and uses.
- MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)- amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester
- Diabetes mellitus is a syndrome characterized by a disordered metabolism and inappropriately high blood sugar (hyperglycemia) resulting from either low levels of the hormone insulin produced by the beta cells of the pancreas or from abnormal resistance to the effects of insulin coupled with inadequate levels of insulin secretion to compensate.
- the World Health Organization recognizes three main forms of diabetes mellitus : type 1 , type 2 and gestational diabetes which have different causes and population distributions.
- Type 1 diabetes is usually due to autoimmune destruction of the pancreatic beta cells.
- Type 2 diabetes is characterized by insulin resistance or reduced insulin sensitivity in target tissues which causes a need for abnormally high amounts of insulin and diabetes may develop when the beta cells cannot meet demand.
- Gestational diabetes is similar to type 2 diabetes in that it involves insulin resistance : the hormones of pregnancy can cause insulin resistance in women genetically predisposed to developing this condition.
- Type 2 diabetes is by far the most common form of diabetes and most often occurs in overweight or obese adults although the prevalence of the disease in adolescent population dramatically increases.
- a main component of type 2 diabetes is insulin resistance at the level of the fat and muscle cells. This means the insulin produced by the pancreas cannot connect with cells to let glucose inside and produce energy. This causes hyperglycemia (high blood glucose). To compensate, the pancreas produces more insulin. The cells sense this increase of insulin and become more resistant, resulting in high glucose levels and often times high insulin levels.
- medication may be used to lower blood glucose levels.
- Type 2 diabetes medications include oral hypoglycemic agents such as metformin, sulphonylureas, thiazolidinediones (rosiglitazone and pioglitazone), meglitinides, sitagliptin, or injectable hormone insulin.
- oral hypoglycemic agents such as metformin, sulphonylureas, thiazolidinediones (rosiglitazone and pioglitazone), meglitinides, sitagliptin, or injectable hormone insulin.
- Metformin or ⁇ /, ⁇ /-dimethylimidodicarbonimidic diamide, is the first-line drug of choice for the treatment of type 2 diabetes in overweight and obese people. Metformin therapy improves insulin sensitivity and is not active in the absence of endogenous or exogenous insulin. Its major effect is to decrease hepatic glucose output and thereby lowering fasting glycaemia. Furthermore, metformin enhances peripheral glucose uptake into the muscle and into adipose tissue.
- Microsomal triglyceride transfer protein (hereinafter referred as MTP) is known to enable the transport of triglyceride, cholesteryl ester and phospholipids such as phosphatidylcholine predominantly in the intestine and in the liver. This indicates that MTP is required for the synthesis of Apo B-containing lipoproteins such as chylomicrons in the gut and VLDL in the liver. It therefore follows that a systemically active MTP inhibitor would inhibit the synthesis of VLDL and LDL, thereby lowering levels of VLDL, LDL, cholesterol and triglyceride in humans.
- MTP Microsomal triglyceride transfer protein
- Compounds capable of inhibiting MTP are believed to be useful in the treatment of disorders such as obesity, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, type 2 diabetes, atherosclerosis and for the reduction of postprandial serum triglyceride plasma levels.
- MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)- amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester is described in WO-02/20501 as compound (230).
- the compound is rapidly metabolised in the plasma, yielding very low systemic plasma concentrations. Therefore it is designed to inhibit predominantly intestinal MTP resulting in the inhibition of triglyceride absorption after the meals but has limited effects on the liver.
- HbAI c glycosylated hemoglobin
- FPG fasting plasma glucose
- HbAIc or glycosylated hemoglobin is a form of hemoglobin that is formed in a non-enzymatic pathway by hemoglobin's normal exposure to high plasma levels of glucose.
- a buildup of HbAIc within the red cells reflects the average level of glucose to which the cell has been exposed during its life cycle.
- Measuring HbAI c assesses the effectiveness of anti-diabetic therapy by monitoring long-term glucose regulation. A more effective treatment of diabetes will result in lower levels of HbAI c.
- metformin and the MTP inhibitor (+)- phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)- acetic acid methyl ester stimulates secretion of incretin hormone glucagon-like peptide (GLP-1 ) which may have beneficial effect on glucose-dependent insulin secretion and also stimulates secretion of peptide YY which induces satiety, thereby producing weight loss and improving insulin sensitivity.
- GLP-1 incretin hormone glucagon-like peptide
- Metformin and the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl- 2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester may be administered in combination simultaneously (e.g. in separate or unitary compositions) or sequentially in either order. In the latter case, the two active ingredients will be administered within a period and in an amount and manner that is sufficient to ensure that an advantageous effect, or even a synergistic effect is achieved. It will be - A -
- administered in combination means that these products are administered to a subject at the same time or within an interval such that there is overlap of an effect of each product on the subject.
- the present invention also relates to products containing as first active ingredient metformin and as second active ingredient the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester, as combined preparations which are suitable for simultaneous or sequential use in the treatment or prophylactic treatment of patients suffering from diabetes mellitus type 2.
- terapéuticaally effective amount means that amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation of the symptoms of the disease or disorder being treated.
- therapeutically effective amount shall mean that amount of the combination of agents taken together or sequentially so that the combined effect elicits the desired biological or medicinal response.
- the therapeutically effective amount of metformin is known to be between 500 mg and 3000 mg per day, usually split in 2 or 3 doses. Extended release formulation tablets may be administered once daily. However in the clinical practice a dose higher than 2000 g/day is given rarely.
- the amount of the metformin and/or the amount of the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]- phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester individually may or may not be therapeutically effective.
- metformin formulation may include an immediate release formulation as well as a sustained or prolonged release (SR) or a novel, extended-release formulation, allowing once daily use.
- SR sustained or prolonged release
- the product containing as first active ingredient metformin and as second active ingredient the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2- carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester, as combined preparations for simultaneous or sequential use in the treatment, control or prevention of diabetes mellitus type 2 may comprise a kit.
- the kit may comprise a container for containing the separate compositions such as a divided bottle or a divided foil packet, wherein each compartment contains a plurality of dosage forms (e.g.
- kits comprising either metformin or the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl- biphenyl-2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester.
- the kit may contain separate compartments each of which contains whole dosage which comprises separate compositions.
- kits for example, a blister pack wherein each individual blister contains two tablets, one tablet comprising metformin, the other comprising the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2- carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester.
- MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2- carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester.
- the kit comprises directions for the administration of the separate components.
- Such instructions would cover situations such as: i. the dosage form in which the components are administered (e.g. oral) ii. when the component parts of the product are administered at different dosage intervals, or iii. when titration of the individual components of the combination is desired by the prescribing physician.
- the container may have deposited thereon a label that describes the contents therein and any appropriate warnings.
- Blister packs are well known in the packaging industry and are widely used for the packaging of pharmaceutical unit dosage forms such as tablets, capsules, and the like. Blister packs generally consist of a sheet of relatively stiff material covered with a foil of a preferably transparent plastic material. During the packaging process recesses are formed in the plastic foil. The recesses have the size and shape of the tablets or capsules to be packed. Next, the tablets or capsules are placed in the recesses and the sheet of relatively stiff material is sealed against the plastic foil at the face of the foil which is opposite from the direction in which the recesses between the plastic foil and the sheet.
- the strength of the sheet is such that the tablets or capsules can be removed from the blister pack by manually applying pressure on the recesses thereby an opening is formed in the sheet at the place of the recess. Tablet(s) or capsule(s) can then be removed by means of the opening.
- a memory aid on the kit, e.g. in the form of numbers next to the tablets or capsules whereby the numbers correspond with the days of the regimen during which the tablets or capsules so specified should be ingested.
- a memory aid is a calendar printed on the card e.g. as follows "First Week, Monday, Tuesday.... etc Second Week, Monday, Tuesday,.... " etc. Other variations of memory aids will be readily apparent.
- a "daily dose” can be a single tablet or capsule or several pills or capsules to be taken on a given day. Also a daily dose of the first compound can consist of one tablet or capsule while a daily dose of the second compound can consist of several tablets or capsules and vice versa. The memory aid should reflect this.
- the present invention is also concerned with pharmaceutical compositions comprising a carrier and as first active ingredient metformin and as second active ingredient the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)- amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester, preferably, each in an amount producing a therapeutic effect in patients with diabetes mellitus type 2.
- the invention also concerns a process for preparing the aforementioned pharmaceutical compositions.
- the products of the present invention comprising as a first active ingredient metformin and as a second active ingredient the MTP inhibitor (+)-phenyl-(4- ⁇ 4-[(4'- trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester as a combined preparation for simultaneous or sequential use or the pharmaceutical compositions of the present invention comprising the combination of metformin and said MTP inhibitor may also be of use in the treatment of obesity or hyperlipidemia.
- the invention is said to relate to the use of a product or pharmaceutical composition according to the invention for the manufacture of a medicament for e.g. the treatment of a mammal, it is understood that such use is to be interpreted in certain jurisdictions as a method of treatment of a mammal, comprising administering to a mammal in need of such treatment, an effective amount of a product or pharmaceutical composition according to the invention.
- the present invention also provides a method of treating or preventing diabetes mellitus type 2 in mammalian subjects, which method comprises the combined administration to the subject of (+)-phenyl-(4- ⁇ 4-[(4'-trifluoromethyl- biphenyl-2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester and metformin.
- the present invention also relates to the use of (+)-phenyl-(4- ⁇ 4-[(4'- trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl ⁇ -piperidin-1-yl)-acetic acid methyl ester for the manufacture of a medicament for combined administration with metformin to improve the efficacy of metformin in the treatment, control or prevention of diabetes mellitus type 2.
- compositions for use in accordance with the invention a therapeutically effective amount of a particular compound, in base or acid addition salt form, as the active ingredient is combined in intimate admixture with a pharmaceutically acceptable carrier, which carrier may take a wide variety of forms depending on the form of preparation desired for administration.
- a pharmaceutically acceptable carrier which carrier may take a wide variety of forms depending on the form of preparation desired for administration.
- These pharmaceutical compositions are desirably in unitary dosage form suitable, for administration orally.
- any of the usual pharmaceutical media may be employed, such as, for example, water, glycols, oils, alcohols and the like in the case of oral liquid preparations such as suspensions, syrups, elixirs and solutions; or solid carriers such as starches, sugars, kaolin, lubricants, binders, disintegrating agents and the like in the case of powders, pills, capsules and tablets. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed.
- Dosage unit form as used in the specification and claims herein refers to physically discrete units suitable as unitary dosages, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier.
- Examples of such dosage unit forms are tablets (including scored or coated tablets), capsules, pills, powder packets, teaspoonfuls, tablespoonfuls and the like, and segregated multiples thereof.
- the starter kit may include a plurality of doses having a constant dose of metformin, such as 250 mg, 500 mg or 100 mg and a variable, increasing dose of MTP inhibitor, for example, 5, 10, 15 mg.
- the starter kit can provide the agents as separate dosage formulations, or alternatively, the starter kit can provide single dosage formulations of two agents.
- exemplary unit dosages are as follows (provided in ratios of metformin : MTP inhibitor as mg dosages): 500:5, 500:10; 500:15, 500:20, 500: 25; 500: 30, 1000:5, 1000:10, 1000:15, 1000:20, 1000:25, 1000: 30, 1500:5, 1500:10, 1500:15, 1500:20, 1500:30, 2000: 5. 2000: 10, 2000: 15, 2000: 20, 2000: 25, 2000: 30.
- HbAIc glycosylated hemoglobin
- the mean body weight loss at Week 12 was 1.88 kg (2%), 1.71 kg (1.0%), 2.80 kg (2.9%) and 3.37 kg (3.6% in the placebo, 5, 10 and 15 mg bid groups, respectively.
- the mean percentage changes from baseline at week 12 in fasting plasma glucose (FPG) in active treatment arms were +0.7%, -2.3%, -6.1%, and -6.0% for the placebo, 5, 10 and 15 mg bid groups, respectively and corresponded to the modest absolute changes from baseline (increase of 0.06 mmol/L and decreases of 0.37. 0.063 and 0.63 mmol/L in placebo, 5, 10 and 15 mg bid dose groups, respectively).
- the magnitude of the observed changes in the active treatment arms are in agreement with to the drop in HbAIc.
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- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Diabetes (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Obesity (AREA)
- Emergency Medicine (AREA)
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Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/811,917 US20100286200A1 (en) | 2008-01-16 | 2009-01-15 | Combination of metformin and an mtp inhibitor |
AU2009204796A AU2009204796B2 (en) | 2008-01-16 | 2009-01-15 | Combination of metformin and an MTP inhibitor |
CA2710815A CA2710815A1 (en) | 2008-01-16 | 2009-01-15 | Combination of metformin and an mtp inhibitor |
EP09701484A EP2244789A2 (en) | 2008-01-16 | 2009-01-15 | Combination of metformin and an mtp inhibitor |
JP2010542626A JP5571000B2 (en) | 2008-01-16 | 2009-01-15 | Combination of metformin and MTP inhibitor |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP08150296 | 2008-01-16 | ||
EP08150296.5 | 2008-01-16 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2009090210A2 true WO2009090210A2 (en) | 2009-07-23 |
WO2009090210A3 WO2009090210A3 (en) | 2009-10-15 |
Family
ID=39493668
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2009/050418 WO2009090210A2 (en) | 2008-01-16 | 2009-01-15 | Combination of metformin and an mtp inhibitor |
Country Status (6)
Country | Link |
---|---|
US (1) | US20100286200A1 (en) |
EP (1) | EP2244789A2 (en) |
JP (1) | JP5571000B2 (en) |
KR (1) | KR20100102631A (en) |
CA (1) | CA2710815A1 (en) |
WO (1) | WO2009090210A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2567959A1 (en) | 2011-09-12 | 2013-03-13 | Sanofi | 6-(4-Hydroxy-phenyl)-3-styryl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003002533A1 (en) * | 2001-06-28 | 2003-01-09 | Pfizer Products Inc. | Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (mtp) and/or apolipoprotein b (apo b) secretion |
US6660300B1 (en) * | 1998-03-19 | 2003-12-09 | Bristol-Myers Squibb Co. | Method of use of a biphasic controlled release delivery system for high solubility pharmaceuticals and method |
EP1806341A2 (en) * | 2000-09-04 | 2007-07-11 | Janssen Pharmaceutica N.V. | (+)Phenyl-(4-{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-piperidin-1-yl)-acetic acid methyl ester as lipid lowering agent |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PE20061245A1 (en) * | 2005-03-30 | 2007-01-06 | Generex Pharm Inc | COMPOSITIONS FOR ORAL TRANSMUCOUS TRANSMISSION OF METFORMIN |
-
2009
- 2009-01-15 US US12/811,917 patent/US20100286200A1/en not_active Abandoned
- 2009-01-15 WO PCT/EP2009/050418 patent/WO2009090210A2/en active Application Filing
- 2009-01-15 KR KR1020107014563A patent/KR20100102631A/en not_active Application Discontinuation
- 2009-01-15 EP EP09701484A patent/EP2244789A2/en not_active Ceased
- 2009-01-15 CA CA2710815A patent/CA2710815A1/en not_active Abandoned
- 2009-01-15 JP JP2010542626A patent/JP5571000B2/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6660300B1 (en) * | 1998-03-19 | 2003-12-09 | Bristol-Myers Squibb Co. | Method of use of a biphasic controlled release delivery system for high solubility pharmaceuticals and method |
EP1806341A2 (en) * | 2000-09-04 | 2007-07-11 | Janssen Pharmaceutica N.V. | (+)Phenyl-(4-{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-piperidin-1-yl)-acetic acid methyl ester as lipid lowering agent |
WO2003002533A1 (en) * | 2001-06-28 | 2003-01-09 | Pfizer Products Inc. | Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (mtp) and/or apolipoprotein b (apo b) secretion |
Non-Patent Citations (2)
Title |
---|
LI J ET AL: "In vitro and in vivo profile of 5-[(4'-trifluoromethyl-biphenyl-2-car bonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), a novel potent MTP inhibitor for obesity" BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB, vol. 17, no. 7, 1 April 2007 (2007-04-01), pages 1996-1999, XP025879636 ISSN: 0960-894X [retrieved on 2007-03-12] * |
WILLIAMS S J ET AL: "Novel microsomal triglyceride transfer protein inhibitors" EXPERT OPINION ON THERAPEUTIC PATENTS 20030401 GB, vol. 13, no. 4, 1 April 2003 (2003-04-01), pages 479-488, XP002485097 ISSN: 1354-3776 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2567959A1 (en) | 2011-09-12 | 2013-03-13 | Sanofi | 6-(4-Hydroxy-phenyl)-3-styryl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
Also Published As
Publication number | Publication date |
---|---|
JP5571000B2 (en) | 2014-08-13 |
KR20100102631A (en) | 2010-09-24 |
WO2009090210A3 (en) | 2009-10-15 |
JP2011509974A (en) | 2011-03-31 |
US20100286200A1 (en) | 2010-11-11 |
EP2244789A2 (en) | 2010-11-03 |
CA2710815A1 (en) | 2009-07-23 |
AU2009204796A1 (en) | 2009-07-23 |
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