105816-04-4 Usage
Uses
Used in Pharmaceutical Industry:
Nateglinide is used as an antidiabetic agent for the treatment of type 2 diabetes mellitus. It is an amino-acid derivative that stimulates insulin secretion, acting as an ATP-sensitive KATP channel blocker. This primary action underlies the mechanism by which Nateglinide markedly stimulates or potentiates insulin secretion from pancreatic beta-cells, depending on glucose concentrations.
Used in Clinical Studies:
Nateglinide is used in clinical studies to demonstrate its safety profile and low potential for hypoglycemia. The pharmacokinetic profile of Nateglinide is consistent with the changes in blood glucose and plasma insulin levels. It is also used to suppress postprandial glucose elevations, unlike other similar agents.
Brand Names:
Nateglinide is marketed under the brand names Starlix (Novartis), Fastic, and Starsis.
Physical and Chemical Properties
White or almost white crystalline powder, odorless, bitter taste. It is soluble in methanol, ethanol, chloroform, dissolved in acetone, ethyl ether, almost insoluble in water. Valid form used in clinic is H-type, mp 137~141 ℃. [Α] D-37.5 °, the maximum UV absorption wavelength in methanol is 252,257,263nm.
The above information is edited by the lookchem of Tian Ye.
Hypoglycemic agents
Nateglinide and mitiglinide, repaglinide are three commonly used non-sulfonylurea oral hypoglycemic agents for insulin secretion,it is successfully developed for the first time by the Japanese company Ajomoto , its chemical structure belongs to carbamoylmethyl-benzoic acid (CMBA), it belongs to D-phenylalanine derivatives, it is a new generation of antidiabetic drugs having amino acid structure ,it is an amino acid derivative prompting insulin secretion, it is also currently the only non-sulfonylureas insulinotropic agent having amino acid structure. The mechanism is mainly through binding the pancreatic β cell sulfonylurea receptor, blocking islet cell ATP-sensitive potassium channels, leading to membrane depolarization, causing the calcium channe lopen to promote insulin secretion. This product is a new type of meal blood glucose regulator, which can effectively control the postprandial blood glucose levels, with rapid onset, short duration of action, low incidence of cardiovascular side effects and hypoglycemia and other characteristics.
Oral bioavailability is 72%, after 15min it can produce insulin secretion effect, Tmax is 0.5~0.9 h, 0.2 h insulin levels achieve peak ,after 1.5 h it is similar to placebo. The plasma protein binding rate is 99%. After reaching plasmapeak , plasma concentrations decline rapidly.T1/2 of oral administration of 120 mg and intravenous injection 60 mg of is 1.5 to 1.7 hours, and the plasma clearance is 7.4 hours. It is metabolized in the liver by isoenzyme CYP2C9 and CYP3A4 way. The main metabolites are products after isomeric oxidation,it can be hydroxyl, diastereomers, isopropyl isomer or unsaturated aliphatic isomers.The main metabolites in plasma and urine are metabolites after the hydroxylation of isopropyl methine family (me-thine carbon) . About 2/3 nateglinide is excreted from the fecal , and the rest is excreted in the urine. Such excretion way is beneficial to elderly Ⅱ diabetes mellitus with renal dysfunction. nateglinide eliminate T1/2 is 1.4 h, because nateglinide T1/2 is short, there is no report yet about the drug accumulation in the body . Long-term use of nateglinide does not produce drug-induced hypoglycemia caused by drug accumulation .It is used for the treatment of diet therapy, exercise therapy and mild to moderate non-insulin dependent (Ⅱ type) diabetes which taking α-glucosidase inhibitor can not control. The results show that: nateglinide can be used more physiologically for meal glucose control, there is less opportunity for contact with insulin and hypoglycemia which allows patients to flexibly plan scheduling mealtimes, which means there is medication while eating, not eating no medication.
Originator
Ajinomoto (Japan)
Biochem/physiol Actions
Nateglinide is a Kir6.2/SUR1 channel inhibitor and antidiabetic. It is selective for the SUR1 subtype, which is found on pancreatic islet cells. Nateglinide evokes KATP channel-dependent insulin secretion (50-200 μM) in the absence and presence of insulin.
Mechanism of action
Approved in the United States in late 2000, nateglinide is a rapidly absorbed insulin secretagogue that has a mechanism of
action similar to that of repaglinide, with effects appearing within 20 minutes following oral dosing.
Bioavailability is 73%,
and it is 98% protein bound, primarily to albumin. Nateglinide is tissue selective, with low affinity for cardiac and skeletal
muscle.
Clinical Use
Treatment of type 2 diabetes in combination with
metformin
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: concentration reduced by rifampicin.
Antifungals: hypoglycaemic effect possibly enhanced
by fluconazole.
Lipid-lowering agents: hypoglycaemic effect possibly
enhanced by gemfibrozil.
Metabolism
It is metabolized in the liver, with 16% excreted in the urine unchanged. The major metabolites are hydroxyl
derivatives (CYP2C9, 70%; CYP3A4, 30%) that are further conjugated to the glucuronide derivatives.
Check Digit Verification of cas no
The CAS Registry Mumber 105816-04-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,5,8,1 and 6 respectively; the second part has 2 digits, 0 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 105816-04:
(8*1)+(7*0)+(6*5)+(5*8)+(4*1)+(3*6)+(2*0)+(1*4)=104
104 % 10 = 4
So 105816-04-4 is a valid CAS Registry Number.
InChI:InChI=1/C19H27NO3/c1-13(2)15-8-10-16(11-9-15)18(21)20-17(19(22)23)12-14-6-4-3-5-7-14/h3-7,13,15-17H,8-12H2,1-2H3,(H,20,21)(H,22,23)/t15-,16-,17-/m1/s1
105816-04-4Relevant articles and documents
METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS
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, (2021/03/13)
In one aspect the invention relates to a method of treatment selected from the group consisting of: (a) treating a symptom such as pain in a subject identified or diagnosed as having Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); (b) treating a symptom such as pain in a subject having dysfunctional TRPM3 ion channel activity; (c) restoring NK cell function in a subject having dysfunctional TRPM3 ion channel activity; and (d) restoring calcium homeostasis in a subject having dysfunctional TRPM3 ion channel activity. The method comprises the step of administering to the subject a therapeutically effective amount of at least one therapeutic compound selected from the group consisting of: (i) an opioid receptor antagonist; (ii) an opioid antagonist; and (iii) a therapeutic compound that restores TRPM3 ion channel activity. In some embodiments the therapeutic compound is naltrexone hydrochloride.
A high-purity process for the preparation of nateglinide
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Paragraph 0028; 0030-0032, (2017/05/04)
A preparation method of high-purity nateglinide comprises the following steps: trans-4-isopropyl-cyclohexanecarboxylic acid is taken as a starting material, acyl chloride obtained by chlorinating sulfoxide chloride reacts with D-phenylalanine, the reaction product is subjected to acid hydrolysis to obtain B-type nateglinide, and then the B-type nateglinide is transformed in ethyl alcohol to obtain H-type nateglinide. The method is simple to operate, the raw materials are easy to obtain, the yield is higher and the product quality is high.
A PROCESS FOR THE PREPARATION OF NATEGLINIDE
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, (2012/01/06)
The present invention relates to a process for the preparation of substantially pure nateglinide of formula (I), substantially free from the cis-isomer and L-enantiomer and preparation of enantiomerically pure nateglinide form B, directly from the hydrolysis of a (-)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine alkyl ester in a ketonic solvent or water or mixture thereof.
A PROCESS FOR THE PREPARATION OF N-[[TRANS-4-(1-METHYLETHYL)CYCLOHEXYL]CARBONYL]-D-PHENYLALANINE
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Page/Page column 18, (2010/10/03)
The present invention is directed to an novel, industrially viable and cost effective process for preparation of substantially pure N-[[trans-4-(l-methylethyl) cyclohexyl] carbonyl]-D- phenylalanine commonly known as Nateglinide.
A NOVEL AND IMPROVED PROCESS FRO THE PREPARATION OF NATEGLINIDE AND ITS POLYMORPH FORM-H
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Page/Page column 10, (2008/06/13)
Nateglinide is prepared by an improved process comprising reaction of trans-4-isopropyl cyclohexane carbonyl chloride with N,O-bis- trimethylsilyl protected D-phenyl alanine to give after aqueous workup, crude nateglinide which is converted to Nateglinide form- H using a mixture of cyclohexane / ethyl acetate. trans-4-isopropyl cyclohexane carbonyl chloride is prepared from trans-4- isopropyl cyclohexane carboxylic acid using oxalyl chloride.
Crystalline form of nateglinide
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, (2008/06/13)
Provided are crystalline forms of nateglinide, labeled Forms A, C, D, F, G, I, J, K, L, M, N, O, P, Q, T, U, V, Y, α, β, γ, δ, ε, σ, θ and Ω, processes for their preparation and processes for preparation of other crystalline forms of nateglinide. Also provided are their pharmaceutical formulations and methods of administration.
USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS
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, (2008/06/13)
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
PROCESS FOR THE PREPARATION OF NATEGLINIDE
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Page/Page column 14-16, (2010/02/15)
One-pot process for the preparation of nateglinide, which process comprises reacting an alkyl ester of D-phenylalanine of formula (II) where R represents C1-4alkyl, typically methyl, either as the free base or in salt form (typically the hydrochloride), with trans-4-isopropylcyclohexanecarboxylic acid of formula (III) where X represents hydroxy or halo, typically chloro, to obtain a C1-4 alkyl ester of nateglinide of formula (IV), preferably the methyl ester of nateglinide followed by hydrolysis to yield nateglinide of formula (I).
Process for the preparation of nateglinide, preferably in b-form
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Page/Page column 7; 8-9, (2010/02/11)
The present invention relates to a process for the preparation of nateglinide, preferably in B-form, substantially free from the H-form, comprising three steps starting from D-phenylalanine methyl ester or a salt thereof.
