- Synthetic method of bepidic acid
-
The invention belongs to the field of medicine synthesis, and relates to a novel synthesis method of a compound bepidic acid. The preparation method comprises the following steps: (1) carrying out primary alkylation on ethyl isobutyrate and 1, 5-dibromopentane under the action of lithium diisopropylamide to generate a compound 1; (2) carrying out alkylation twice on dibenzyl malonate and the compound 1 under the action of sodium hydride to generate a compound 2; (3) removing benzyl from the compound 2 under the action of Pd/C and hydrogen to obtain a compound 3; (4) carrying out electrochemical reaction on the compound 3 in a methanol solution of methanol and ammonia to obtain a compound 4; (5) finally carrying out sodium borohydride hydrolysis and potassium hydroxide hydrolysis on the compound 4, and acidifying to obtain the final bepidic acid. The method is carried out under electrochemical conditions, is mild in conditions and high in efficiency, and is suitable for industrial production.
- -
-
Paragraph 0033-0034; 0040-0041; 0047-0048
(2021/03/13)
-
- Synthesis of bempedoic acid through electrochemical decarboxylation of dialkylated malonic acid
-
Bempedoic acid is a small-molecule inhibitor of adenosine triphosphate-citrate lyase (ACL) that is effective in the treatment of hypercholesterolemia and hypertension. In this paper, a new, six-step synthesis of bempedoic acid with 42% overall yield is reported. Ketone formation by electrochemical decarboxylation of dialkylated malonic acid is introduced as the key step of this process. This method uses mild conditions and its high efficiency makes it potentially suitable for industrial production.
- Xu, Zhimin,Zheng, Yue,Tian, Lifang,Wang, Yahui
-
p. 3608 - 3612
(2021/05/21)
-
- Synthesis method of 8-hydroxy-2, 2, 14, 14-tetramethyl pentadecanedioic acid
-
The invention provides a synthesis method for preparing 8-hydroxy-2, 2, 14, 14-tetramethyl pentadecanedioic acid, which comprises the step of carrying out addition reaction on a compound III and a compound IV to obtain a compound II. The method has the advantages of cheap and easily available raw materials and short steps, and can greatly reduce the production cost; the operation is simple, and industrial production is facilitated; and the quality of reaction products in each step is controllable, and the obtained product is high in purity and small in single impurity.
- -
-
Paragraph 0047-0050
(2021/09/11)
-
- MACROCYCLIC INHIBITORS OF PEPTIDYLARGININE DEIMINASES
-
The present disclosure relates to novel compounds for use in therapeutic treatement of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.
- -
-
Page/Page column 259; 319
(2021/11/06)
-
- Method for synthesizing ethyl-2,2-dimethyl-7-bromoheptanoate
-
The invention discloses a method for synthesizing ethyl-2,2-dimethyl-7-bromoheptanoate. The method comprises the following steps: introducing ethyl isobutyrate and an organic alkali reagent into a continuous flow reactor through a metering pump; preparing an ethyl isobutyrate lithium salt solution through pre-cooling, mixing and reacting; continuously reacting the solution with 1,5-dibromopentanein a continuous flow reactor, completing quenching operation through a quenching post-treatment module, and finally performing post-treatment to obtain a substituted product, namely ethyl-2,2-dimethyl-7-bromoheptanoate. The method has the advantages that conditions are accurately controlled, selectivity is good, the amplified production of the product becomes possible, operation is simple, convenient and safe, yield is high, a reaction rate is high, etc.; and huge practical values are obtained in the aspects of improving production safety, improving the yield and output of ethyl-2,2-dimethyl-7-bromoheptanoate and improving production efficiency.
- -
-
Paragraph 0030; 0033-0075
(2020/09/30)
-
- Synthesis method of ethyl 2, 2-dimethyl-7-bromoheptanoate, and product obtained by synthesis
-
The invention relates to the technical field of medicine synthesis, and especially relates to a synthesis method of ethyl 2, 2-dimethyl-7-bromoheptanoate, and a product obtained through synthesis. Thesynthesis method comprises the following step: by taking ethyl isobutyrate, 1, 5-dibromopentane and sodium hydride as initial raw materials, reacting for 20-25 hours at 5-85 DEG C in the presence ofa solvent to obtain ethyl 2, 2-dimethyl-7-bromoheptanoate, wherein the molar ratio of the ethyl isobutyrate to the 1, 5-dibromopentane to the sodium hydride is 1: (1-1.2): (1-1.2); and the solvent isN, N-dimethyl propenyl urea. According to the method, a lithium reagent which is strong in reaction activity and difficult to control is effectively prevented from being used as a reducing agent and is replaced by a strong alkaline substance sodium hydride, so that the synthesis method is simple to operate and easy for industrial production, and the problems of high risk, high cost and difficultyin industrial production due to the use of the lithium reagent in the prior art are effectively solved.
- -
-
Paragraph 0049-0087
(2020/12/29)
-
- Substituted pentadecanedioic acid compound and pharmaceutical composition and application thereof
-
The invention provides a substituted pentadecanedioic acid compound, a pharmaceutical composition comprising the substituted pentadecanedioic acid compound and application of the substituted pentadecanedioic acid compound and the pharmaceutical composition. The compound refers to a compound shown as a formula (I), or a pharmaceutically acceptable salt of the compound, a prodrug, a hydrate or a solvate, a crystal form, a stereoisomer or an isotope variant. The compound can be used for treatment or prevention of cardiovascular diseases or dyslipidemia and has excellent pharmacokinetic properties.
- -
-
Paragraph 0161-0166
(2019/08/07)
-
- FLAVIN DERIVATIVES
-
The present invention relates novel flavin derivatives and other flavin derivatives, their use and compositions for use as riboswitch ligands and/or anti-infectives. The invention also provides method of making novel flavin derivatives.
- -
-
Page/Page column 286
(2010/04/03)
-
- POLYALKYLENE OXIDES HAVING HINDERED ESTER-BASED BIODEGRADABLE LINKERS
-
The present invention provides polymeric delivery systems including hindered ester moieties. Methods of making the polymeric delivery systems and methods of treating mammals using the same are also disclosed.
- -
-
Page/Page column 57
(2008/06/13)
-
- HINDERED ESTER-BASED BIODEGRADABLE LINKERS FOR OLIGONUCLEOTIDE DELIVERY
-
The invention provides hindered ester-based biodegradable linkers for the delivery of oligonucleotides in vivo, as well as method of making and using the same.
- -
-
Page/Page column 47-48
(2008/06/13)
-
- KETONE COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES
-
The present invention relates to novel ketone compounds, compositions comprising ketone compounds, and methods useful for treating and preventing cardiovascular diseases, dyslipidemias, dysproteinemias, and glucose metabolism disorders comprising administering a composition comprising a ketone compound. The compounds, compositions, and methods of the invention are also useful for treating and preventing Alzheimer's disease, Syndrome X, peroxisome proliferator activated receptor-related disorders, septicemia, thrombotic disorders, obesity, pancreatitis, hypertension, renal disease, cancer, inflammation, and impotence. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.
- -
-
Page/Page column 224; 285
(2010/02/13)
-
- HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES
-
The present invention relates to novel hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, pancreatitius, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, metabolic syndrome disorders (e.g., Syndrome X), thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.
- -
-
-
- Long hydrocarbon chain keto diols and diacids that favorably alter lipid disorders in vivo
-
Keto-substituted hydrocarbons with 11-19 methylene and bis-terminal hydroxyl and carboxyl groups have been synthesized and evaluated in both in vivo and in vitro assays for their potential to favorably alter lipid disorders including metabolic syndrome. Compounds were assessed for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes as well as for their effects on lipid and glycemic variables in obese female Zucker fatty rats [Crl:(ZUC)-faBR] following 1 and 2 weeks of oral administration. The most active compounds were found to be symmetrical with four to five methylene groups separating the central ketone functionality and the gem dimethyl or methyl/aryl substituents. Furthermore, biological activity was found to be greatest in both in vivo and in vitro assays for the tetramethyl-substituted keto diacids and diols (e.g., 10c, 10g, 14c), and the least active were shown to be the bis(arylmethyl) derivatives (e.g., 10e, 10f, 14f). Compound 14c dose-dependently elevated HDL-cholesterol, reduced triglycerides, and reduced NEFA, with a minimum effective dose of 30 mg/kg/day. Compound 10g dose-dependently modified non-HDL-cholesterol, triglycerides, and nonesterified fatty acids, with a minimum effective dose of 10 mg/kg/day. At this dose, compound 10g elevated HDL-cholesterol levels 2-3 times higher than pretreatment levels, and a dose-dependent reduction of fasting insulin and glucose levels was observed.
- Mueller, Ralf,Yang, Jing,Duan, Caiming,Pop, Emil,Geoffroy, Otto J.,Zhang, Lian Hao,Huang, Tian-Bao,Denisenko, Sergey,McCosar, Bruce H.,Oniciu, Daniela C.,Bisgaier, Charles L.,Pape, Michael E.,Freiman, Catherine Delaney,Goetz, Brian,Cramer, Clay T.,Hopson, Krista L.,Dasseux, Jean-Louis H.
-
p. 6082 - 6099
(2007/10/03)
-
