- Design, synthesis, biological evaluation and computational study of novel triazolo [4,3-a]pyrazin analogues
-
The triazolo [4,3-a]pyrazin analogues are of interest due to their potential activity against various infectious and non-infectious disease. In search of suitable potent drug candidate, we report here the design, synthesis, characterization, biological activities and computation study of novel triazolo [4,3-a]pyrazin analogues. The synthesized molecules were characterized by various spectroscopic studies such as IR, Mass, 1H NMR, 13C NMR and elemental analysis. The newly synthesized compounds were evaluated for their in vitro biological activities such as anti-malarial, anti-tuberculosis, anti-bacterial and anti-fungal activities against plasmodium falciparum, H37Rv, various bacterial and fungal strains, respectively. The molecular docking study was carried out with enzyme aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum to analyze their binding orientation in the active site of the aspartic proteinase enzyme. The best docking complex was subjected to molecular dynamics simulation to illustrate the stability of these complexes and the most prominent interactions during the simulated trajectory. We have also calculated ADMET properties of all the synthesized compounds to predict the pharmacokinetic properties for the selection of the active and bioavailability of compounds.
- Jethava, Divya J.,Acharya, Prachi T.,Vasava, Mahesh S.,Bhoi, Manoj N.,Bhavsar, Zeel A.,Rathwa, Sanjay K.,Rajani, Dhanji P.,Patel, Hitesh D.
-
p. 168 - 192
(2019/03/04)
-
- plants the deuterium mark sitagliptin a process for the preparation of
-
The present invention discloses a method for preparing deuterium-labeled sitagliptin. The deuterium-labeled sitagliptin-D4 is synthesized by an eight-step reaction with hydrazine hydrate as a starting material and ethylene-D4 as a deuterium-labeled initiator. The optimal preparation steps and reaction conditions are screened through a plurality of experiments in the invention and the entire process is reasonable in design and high in operability. The deuterium-labeled sitagliptin prepared by the invention has purity of over 98% and the yield up to 70% or more, and isotopic abundance is greater than 99%. The deuterium-labeled sitagliptin prepared by the invention can provide test samples for a research on the metabolic mechanism of sitagliptin and has important application value.
- -
-
Paragraph 0040-0043
(2017/04/06)
-
- Radical-based route to 2-(trifluoromethyl)-1,3,4-oxadiazoles and trifluoromethyl -substituted polycyclic 1,2,4-triazoles and dihydrofurans
-
O-Ethyl S-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl xanthate was readily prepared on a large scale and shown to undergo very efficient intermolecular radical additions to unactivated alkenes. The products were further elaborated by exploiting both
- Qin, Ling,Zard, Samir Z.
-
supporting information
p. 1577 - 1580
(2015/03/30)
-
- PROCESSES FOR THE PREPARATION OF SITAGLIPTIN AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
-
There is provided salts and polymorphs of sitagliptin, processes for the preparation thereof, and pharmaceutical compositions comprising the same.
- -
-
Page/Page column 26
(2009/08/14)
-
- DODECYLSULFATE SALT OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR
-
The dodecylsulfate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-l-(2,4,5-trifluorophenyl) butan-2-amine is a potent inhibitor of dipeptidyl peptidase-IV and is useful for the treatment of Type 2 diabetes. The invention also relates to a crystalline anhydrate of the dodecylsulfate salt as well as a process for its preparation, pharmaceutical compositions containing this novel form and methods of use for the treatment of Type 2 diabetes, hyperglycemia, insulin resistance, and obesity.
- -
-
Page/Page column 8-9
(2008/06/13)
-
- COMBINATION OF A DIPEPTIDYL PEPTIDASE-4 INHIBITOR AND AN ANTI-HYPERTENSIVE AGENT FOR THE TREATMENT OF DIABETES AND HYPERTENSION
-
The present invention relates to pharmaceutical compositions comprising a combination of a particular dipeptidyl peptidase-4 (DPP-4) inhibitor and an anti-hypertensive agent selected from the group consisting of an angiotensin II receptor antagonist and an angiotensin converting enzyme inhibitor, kits containing such combinations and methods of using such compositions for the treatment of diabetes, diabetes-related disorders, hypertension, and hypertension-related disorders.
- -
-
Page/Page column 32-33
(2008/06/13)
-
- PROCESS TO CHIRAL BETA AMINO ACID DERIVATIVES BY ASYMMETRIC HYDROGENATION
-
The present invention relates to a process for the efficient preparation of enantiomerically enriched beta amino acid derivatives which are useful in the asymmetric synthesis of biologically active molecules. The process comprises an enantioselective hydrogenation of a prochiral beta amino acrylic acid derivative substrate in the presence of an ammonium salt and a transition metal precursor complexed with a chiral ferrocenyl diphosphine ligand.
- -
-
Page/Page column 11-12
(2008/06/13)
-
- AMINOCYCLOHEXANES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
-
The present invention is directed to novel substituted aminocyclohexanes which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DPP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
- -
-
Page/Page column 41
(2008/06/13)
-
- COMBINATION OF DIPEPTIDYL PEPTIDASE-IV INHIBITOR AND A CANNABINOID CB1 RECEPTOR ANTAGONIST FOR THE TREATMENT OF DIABETES AND OBESITY
-
The present invention relates to pharmaceutical compositions comprising a combination of a particular dipeptidyl peptidase-IV (DPP-IV) inhibitor and a particular cannabinoid CB?1#191 receptor antagonist/inverse agonist, kits containing such combinations and methods of using such compositions for the treatment of diabetes, diabetes associated with obesity, diabetes-related disorders, obesity, and obesity-related disorders.
- -
-
Page/Page column 41
(2008/06/13)
-
- AMORPHOUS FORM OF A PHOSPHORIC ACID SALT OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR
-
The present invention relates to a novel amorphous form of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-a mine as well as a process for its preparation, pharmaceutical compositions containing this novel form, and methods of use of the novel form and pharmaceutical compositions for the treatment of diabetes, obesity, and high blood pressure.
- -
-
Page/Page column 8-9
(2008/06/13)
-
- COMBINATION OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR AND A DUAL PPAR AGONIST FOR THE TREATMENT OF DIABETES AND OBESITY
-
The present invention relates to pharmaceutical compositions comprising a combination of a particular dipeptidyl peptidase-IV (DPP-IV) inhibitor and a particular PPAR-α/γ dual agonist, kits containing such combinations and methods of using such compositions for the treatment of diabetes, diabetes associated with obesity, diabetes-related disorders, obesity, and obesity-related disorders.
- -
-
Page/Page column 17
(2010/11/24)
-
- PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED BETA AMINO ACID DERIVATIVES
-
The present invention relates to a process for the efficient preparation of enantiomerically enriched beta amino acid derivatives wherein the amino group is unprotected. The product chiral beta amino acid derivatives are useful in the asymmetric synthesis of biologically active molecules. The process comprises an enantioselective hydrogenation of an amine-unprotected prochiral beta-amino acrylic acid or derivative thereof in the presence of a rhodium metal precursor complexed with a chiral mono- or bisphosphine ligand.
- -
-
Page/Page column 19-21
(2008/06/13)
-
- NOVEL CRYSTALLINE FORMS OF A PHOSPHORIC ACID SALT OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR
-
The present invention relates to crystalline anhydrate polymorphs of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-alpha]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine as well as a process for their preparation, pharmaceutical compositions containing these novel forms, and methods of use of the novel forms and pharmaceutical compositions for the treatment of diabetes, obesity, and high blood pressure. The invention also concerns novel crystalline solvates of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-alpha]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine as well as a crystalline desolvated polymorph and their use for the preparation of the anhydrate polymorphs of the present invention.
- -
-
Page/Page column 9-10
(2008/06/13)
-
- PHOSPHORIC ACID SALT OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR
-
The dihydrogenphosphate salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine is a potent inhibitor of dipeptidyl peptidase-IV and is useful for the prevention and/or treatment of non-insulin dependent diabetes mellitus, also referred to as type 2 diabetes. The invention also relates to a crystalline monohydrate of the dihydrogenphosphate salt as well as a process for its preparation, pharmaceutical compositions containing this novel form and methods of use for the treatment of diabetes, obesity, and high blood pressure.
- -
-
-
- NOVEL CRYSTALLINE SALTS OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR
-
Novel crystalline salts of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-α amine are potent inhibitors of dipeptidyl peptidase-IV and are useful for the treatment of non-insulin dependent (Type 2) diabetes mellitus. The invention also relates to pharmaceutical compositions containing these novel salts, processes to prepare these salts and their pharmaceutical compositions as well as uses thereof for the treatment of Type 2 diabetes.
- -
-
Page/Page column 9-10
(2010/02/13)
-
- NOVEL CRYSTALLINE FORM OF A PHOSPHORIC ACID SALT OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR
-
The present invention relates to a novel crystalline anhydrate polymorph of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-a mine as well as a process for their preparation, pharmaceutical compositions containing this novel form, and methods of use of the novel form and pharmaceutical compositions for the treatment of diabetes, obesity, and high blood pressure.
- -
-
Page/Page column 7-8
(2008/06/13)
-
- Synthesis of [1,2,4]triazolo[4,3-α]piperazines via highly reactive chloromethyloxadiazoles
-
(Chemical Equation Presented) A concise, modular approach for the synthesis of [1,2,4]triazolo[4,3-α]piperazines via condensation of highly reactive chloromethyloxadiazoles with ethylenediamines is described. NMR studies of this reaction provide evidence that suggests a novel activation mechanism for electron-deficient chloromethyloxadiazoles.
- Balsells, Jaume,DiMichele, Lisa,Liu, Jinchu,Kubryk, Michele,Hansen, Karl,Armstrong III, Joseph D.
-
p. 1039 - 1042
(2007/10/03)
-
- PROCESS FOR THE PREPARATION OF CHIRAL BETA AMINO ACID DERIVATIVES BY ASYMMETRIC HYDROGENATION
-
The present invention relates to a process for the efficient preparation of enantiomerically enriched beta amino acid derivatives which are useful in the asymmetric synthesis of biologically active molecules. The process comprises an enantioselective hydrogenation of a prochiral beta amino acrylic acid derivative substrate in the presence of a transition metal precursor complexed with a chiral ferrocenyl diphosphine ligand.
- -
-
-
- PROCESS TO BETA-KETOAMIDE INTERMEDIATES TO DIPEPTIDYL PEPTIDASE INHIBITORS
-
A novel process is provided for the preparation of beta-ketoamide intermediates which are useful in the synthesis of dipeptidyl peptidase-IV inhibitors for the treatment of type 2 diabetes. Also provided are useful intermediates obtained from the process.
- -
-
-
- PROCESS TO TETRAHYDROTRIAZOLOPYRAZINES AND INTERMEDIATES
-
A novel process is provided for the preparation of substituted-5,6,7,8-tetrahydro[1,2,4]-triazolo[4,3-alpha]pyrazines which are useful in the synthesis of dipeptidyl peptidase-IV inhibitors for the treatment of Type 2 diabetes. Also provided are useful intermediates obtained from the process.
- -
-
-
- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF BETA-AMINO ACID AMIDE DIPEPTIDYL PEPTIDASE-IV INHIBITORS
-
A novel process is provided for the preparation of chiral beta-amino acid amide inhibitors of the dipeptidyl peptidase-IV and the useful intermediates obtained therein. The products resulting from the instant process are inhibitors of dipeptidyl peptidase-IV and thereby useful for the treatment of Type 2 diabetes.
- -
-
-
- 2-hydroxybenzophenone hydrazides and derivatives thereof
-
Hydrazide functionalized 2-hydroxybenzophenone ultraviolet light and heat stabilizers and derivatives are disclosed having the general formula: STR1 wherein R1, R2, R3, R4, R5, R6, X, Y, Z,
- -
-
-
- Oxyformamidates
-
Compounds of the formula STR1 WHEREIN A is a linking group, X is an O--CO-- or --SO2 -- group and n is at least 2, are prepared from the corresponding N',N'-disubstituted hydrazides by quaternization and treatment with alkali or reaction with an alkylene epoxide or from the corresponding compound wherein n = 1 and A is a polymerizable group by polymerization. The compounds are unstable to heat and may be used as cross-linking agents for polymers or as chain-extending agents, bonding agents or adhesives.
- -
-
-