- Microwave-Assisted Synthesis and Antituberculosis Screening of Some 4-((3-(Trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-l)methyl)benzenamine Hybrids
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In the present investigation, a series of 4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)benzenamine analogs 6a–o were synthesized and characterized by IR, NMR (1H and 13C), and mass spectra. All newly synthesized compounds 6a–o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a–o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC50: 1.82?μg/mL), 6j (IC50: 1.02?μg/mL), and 6k (IC50: 1.59?μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC90 value of 16.02?μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M.?tuberculosis that can be explored further for the potential antitubercular drug.
- Patil, Yogesh,Shingare, Ramesh,Choudhari, Amit,Sarkar, Dhiman,Madje, Balaji
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- Urea and thiourea derivatives of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine: Synthesis, characterization, antimicrobial activity and docking studies
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An efficient and robust synthetic procedure was developed primarily for the synthesis of a precursor compound; 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine (11), from 2-chloropyrazine (7) through the chemical transformations such as hydrazine substitution, trifluoroacetyl group induction, cyclization and pyrazine ring reduction. A new series of urea derivatives 13a-e and thiourea derivatives 13f-j of compound 11 have been synthesized and the structures of all the compounds were confirmed using spectroscopic analyses such as IR, 1H NMR, 13C NMR, LC-MS and HRMS. The newly synthesized compounds were screened for their in vitro antimicrobial activity against five bacteria and two fungi, in which compounds 13d, 13i and 13j displayed potential activity against bacterial strains and 13a, 13d, 13g and 13j against fungal strains with the MIC values in the range of 6.25–25.0 μg/mL. An overall comparison of the activity results revealed that thiourea derivatives contain better activity than that of urea compounds. Molecular docking studies on poly (ADP-ribose) polymerase 15 (ARTD7, BAL3) demonstrated that all the synthesized compounds possess significant binding energies (-8.1 to -9.8 kcal/mol) with no adverse effect in the active site of protein.
- Mannam, Madhava Rao,Devineni, Subba Rao,Pavuluri, Chandra Mouli,Chamarthi, Naga Raju,Kottapalli, Raja Sekhara P.
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- Mannich base derivatives of 1,2,4-triazocyclo [4,3-alpha] condensed piperazine as well as preparation method and application of Mannich base derivatives
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Mannich base derivatives of 1,2,4-triazocyclo [4,3-alpha] condensed piperazine have the structural formula shown as general formula I in the specification. The Mannich base derivatives have the following advantages: according to a preparation method, substitutive derivatives are prepared from 1,2,4-triazocyclo [4,3-alpha] condensed piperazine by introducing different substituent groups into 1,2,4-triazocyclo [4,3-alpha] condensed piperazine, a novel structure with higher biological activity is discovered, novel structure-activity relationship and biological activity laws are summarized; the prepared Mannich base derivatives have higher bactericidal activity and herbicidal activity, have high in-vitro inhibitory activity for plant pathogens such as fusarium wilt pathogen of cucumbers, cercospora arachidicola, Macrophoma kawatsukai, rhizoctonia cerealis pathogen, alternaria solani of tomatoes, gibberella zeae and the like and can be used for controlling fungus and weed damage to plants, and bactericidal or herbicidal composition further comprises a vector acceptable in agriculture, forestry and hygiene.
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Paragraph 0036
(2017/08/02)
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- Methods for Treating Cognitive Disorders Using Inhibitors of Histone Deacetylase
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This disclosure relates to compounds for the inhibition of histone deacetylase and treatment of a cognitive disorder or deficit. More particularly, the disclosure provides for compounds of formula (I) wherein Q, J, L and Z are as defined in the specification.
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Paragraph 0715
(2017/01/23)
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- BETA-AMINO HETEROCYCLIC DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-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.
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Paragraph 0208
(2015/12/30)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0281-0282
(2014/08/19)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 00199
(2013/06/05)
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- Exploring the unexplored practical and alternative synthesis of 3-(trifluoromethyl)-triazolopiperazine the key intermediate for Sitagliptin
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The practical synthesis of 3-(trifluoromethyl)-triazolopiperazine the key intermediate of Sitagliptin and 3-(trifluoromethyl)-triazolopyridine was carried out employing industrially feasible transformations. The other advantage of this method is the new environment friendly approach to synthesize triazolopiperazine and triazolopyridines by eliminating the commonly used trifluoroacetic anhydride and polyphosphoric acid.
- Nitlikar, Lakshmikant H.,Darandale, Sunil N.,Shinde, Devanand B.
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p. 348 - 352
(2013/07/26)
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- FUSED TRIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel fused triazole derivatives 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.
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Page/Page column 47
(2008/06/13)
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- First generation process for the preparation of the DPP-IV inhibitor sitagliptin
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A new synthesis of sitagliptin (MK-0431), a DPP-IV inhibitor and potential new treatment for type II diabetes, suitable for the preparation of multi-kilogram quantities is presented. The triazolopyrazine fragment of sitagliptin was prepared in 26% yield over four chemical steps using a synthetic strategy similar to the medicinal chemistry synthesis. Key process developments were made in the first step of this sequence, the addition of hydrazine to chloropyrazine, to ensure its safe operation on a large scale. The beta-amino acid fragment of sitagliptin was prepared by asymmetric reduction of the corresponding beta-ketoester followed by a two-step elaboration to an N-benzyloxy beta-lactam. Hydrolysis of the lactam followed by direct coupling to the triazolopiperazine afforded sitagliptin after cleavage of the N-benzyloxy group and salt formation. The overall yield was 52% over eight steps.
- Hansen, Karl B.,Balsells, Jaume,Dreher, Spencer,Hsiao, Yi,Kubryk, Michele,Palucki, Michael,Rivera, Nelo,Steinhuebel, Dietrich,Armstrong III, Joseph D.,Askin, David,Grabowski, Edward J. J.
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p. 634 - 639
(2012/12/25)
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- (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-amine: A potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
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A novel series of β-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (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-amine (1) is a potent, orally active DPP-IV inhibitor (IC50 = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.
- Kim, Dooseop,Wang, Liping,Beconi, Maria,Eiermann, George J.,Fisher, Michael H.,He, Huaibing,Hickey, Gerard J.,Kowalchick, Jennifer E.,Leiting, Barbara,Lyons, Kathryn,Marsilio, Frank,McCann, Margaret E.,Patel, Reshma A.,Petrov, Aleksandr,Scapin, Giovanna,Patel, Sangita B.,Roy, Ranabir Sinha,Wu, Joseph K.,Wyvratt, Matthew J.,Zhang, Bei B.,Zhu, Lan,Thornberry, Nancy A.,Weber, Ann E.
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p. 141 - 151
(2007/10/03)
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- 3-AMINO-4-PHENYLBUTANOIC ACID DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-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.
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Page/Page column 87
(2010/02/07)
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