143317-59-3Relevant articles and documents
THIAZOLE DERIVATIVES AS PROTEIN SECRETION INHIBITORS
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Paragraph 00260; 00319, (2020/09/12)
Provided herein are secretion inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same, wherein the compound has a structure of Formula (I), (II), or (III).
Combining prolinamides with 2-pyrrolidinone: Novel organocatalysts for the asymmetric aldol reaction
Vlasserou, Ismini,Sfetsa, Maria,Gerokonstantis, Dimitrios-Triantafyllos,Kokotos, Christoforos G.,Moutevelis-Minakakis, Panagiota
, p. 2338 - 2349 (2018/04/06)
Peptides and especially prolinamides have been identified as excellent organocatalysts for the aldol reaction. The combination of prolinamides with derivatives bearing the 2-pyrrolidinone scaffold, deriving from pyroglutamic acid, led to the identification of novel organocatalysts for the intermolecular asymmetric aldol reaction. The new hybrids were tested both in organic and aqueous media. Among the compounds tested, 22 afforded the best results in petroleum ether, while 25 afforded the products in brine in high yields and selectivities. Then, various ketones and aldehydes were utilized and the products of the aldol reaction were obtained in high yields (up to 100%) with excellent diastereo- (up to 97:3 dr) and enantioselectivities (up to 99% ee).
Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids
Misra, Ankita,Anil Kumar,Jain, Manish,Bajaj, Kirti,Shandilya, Shyamali,Srivastava, Smriti,Shukla, Pankaj,Barthwal, Manoj K.,Dikshit, Madhu,Dikshit, Dinesh K.
, p. 1 - 12 (2016/01/29)
N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited
3,7-DIAZABICYCLO[3.3.1 ]NONANE CARBOXAMIDES AS ANTITHROMBOTIC AGENTS
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Page/Page column 14; 15, (2015/04/15)
The present invention relates to the 3,7-diazabicyclo[3.3.1]nonane carboxamides and process for preparation thereof. The present invention further relates to the compounds of general formula (1) possessing anti-thrombotic (anti-platelet) activities. The invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors both in vitro and in vivo. Further, invention also relates these class of compounds exhibiting anti-platelet efficacy through dual mechanism inhibited both collagen as well as U46619 (thromboxane receptor agonist) induced platelet aggregation. General formula (1) Wherein, R' is; wherein R is selected from alkyl, acyl, tosyl, tert-butyloxycarbonyl, araalkyl or substituted araalkyl groups; R'' is selected preferably from halogen, cyano, lower alkyl, aryl, substituted aryl, and tosyl groups; R1 is selected from hydrogen and lower alkyl groups; R2 is selected from lower alkyl and aryl groups; R3 is selected from tert-butyloxycarbonyl and bezyloxycarbonyl groups; n = 0,1.
Synthesis and identification of chiral aminomethylpiperidine carboxamides as inhibitor of collagen induced platelet activation
Anil Kumar,Misra, Ankita,Siddiqi, Tanveer Irshad,Srivastava, Stuti,Jain, Manish,Bhatta, Rabi Sankar,Barthwal, Manoj,Dikshit, Madhu,Dikshit, Dinesh K.
, p. 456 - 472 (2014/06/09)
A series of chiral lactam carboxamides of aminomethylpiperidine were synthesized and investigated for the collagen induced in vitro anti-platelet efficacy and collagen plus epinephrine induced in vivo pulmonary thromboembolism. The compound 31a (30 μM/kg) displayed a remarkable antithrombotic efficacy (60% protection) which was sustained for more than 24 h and points to its excellent bioavailability. The compounds 31a (IC50 = 6.6 μM) and 32a (IC50 = 37 μM), as well as their racemic mixture 28i (IC50 = 16 μM) significantly inhibited collagen-induced human platelet aggregation in vitro. Compound 34c displayed dual mechanism of action against both collagen (IC50 = 3.3 μM) and U46619 (IC50 = 2.7 μM) induced platelet aggregation. The pharmacokinetic study of 31a indicated very faster absorption, prolonged and constant systemic exposure and thereby exhibiting better therapeutic response.
An efficient and straight forward synthesis of (5S)-1-benzyl-5-(1H- imidazol-1-ylmethyl)-2-pyrrolidinone (MM1): A novel antihypertensive agent
Prasad, Jagdish,Pathak, Manoher Bhushan,Panday, Sharad Kumar
experimental part, p. 321 - 324 (2012/08/28)
(5S)-1-benzyl-5-(1H-imidazol-1-ylmethyl)-2-pyrrolidinone and its closely related analog was synthesized from (S)-pyroglutaminol and imidazole or substituted imidazole using Mitsunobu reaction as the key step. Springer Science+Business Media, LLC 2010.
Synthesis, in silico docking experiments of new 2-pyrrolidinone derivatives and study of their anti-inflammatory activity
Moutevelis-Minakakis, Panagiota,Papavassilopoulou, Eleni,Michas, George,Georgikopoulou, Kalliopi,Ragoussi, Maria-Eleni,Neophytou, Niki,Zoumpoulakis, Panagiotis,Mavromoustakos, Thomas,Hadjipavlou-Litina, Dimitra
experimental part, p. 2888 - 2902 (2011/06/17)
A new class of 2-pyrrolidinone derivatives was designed, synthesized, and tested for their antioxidant and anti-inflammatory activities. The compounds were evaluated for their inhibitory activity against LOX. The most potent among them, 14d [IC50 0.08 (±0.005) mM], and 14e [IC50 0.0705 (±0.003) mM], were also tested in vivo. The compound 14d induced equipotent inhibition against rat paw edema, which is very close to the effect produced by the commonly used standard, namely indomethacin (47%). The LOX inhibitory activity of the compound 14e proceeds in parallel to the % inhibitory value of lipid peroxidation meaning that this LOX inhibitory activity is supported by the lipid peroxidation inhibition. The molecular features that govern their bioactivity were explored through in silico docking experiments. The results showed that acidic moieties must be placed in certain distance and orientation in the active site of LOX enzyme in order to productively exhibit inhibitory activity. In addition, the 2-pyrrolidinone template significantly contributes in the inhibitory properties of the new compounds.
Straightforward and facile approach toward the n-derivatization of pyroglutamates through mitsunobu reaction: Synthesis of N-alkyl/N-acyl pyroglutamates
Panday, Sharad Kumar,Prasad, Jagdish,Pathak, Manoher Bhushan
experimental part, p. 3654 - 3661 (2011/10/09)
Pyroglutamates have been acknowledged as useful chiral synthons for the synthesis of many bioactive natural products, ACE inhibitors, and conformationally constrained peptides. Though the reactivity differences between two differential carbonyl groups have been well exploited, there is still a dearth of publications on the N-alkylation/acylation of native pyroglutamate as such, due to the relatively low reactivity of NH of pyroglutamates. In the present communication, we report for the first time a simple and efficient methodology for the N-alkylation/acylation of pyroglutamate via Mitsunobu reaction. Copyright Taylor & Francis Group, LLC.
Synthesis, binding studies and in vivo biological evaluation of novel non-peptide antihypertensive analogues
Mavromoustakos,Moutevelis-Minakakis,Kokotos,Kontogianni,Politi,Zoumpoulakis,Findlay,Cox,Balmforth,Zoga,Iliodromitis
, p. 4353 - 4360 (2007/10/03)
AT1 antagonists (SARTANs) constitute the last generation of drugs for the treatment of hypertension, designed and synthesized to mimic the C-terminal segment of the vasoconstrictive hormone angiotensin II (AngII). They exert their action by blocking the binding of AngII on the AT1 receptor. Up to date eight AT1 antagonists have been approved for the regulation of high blood pressure. Although these molecules share common structural features and are designed to act under the same mechanism, they have differences in their pharmacological profiles and antihypertensive efficacy. Thus, there is still a need for novel analogues with better pharmacological and financial profiles. An example of a novel synthetic non peptide AT1 antagonist which devoids the classical template of SARTANs is MM1. In vivo studies showed that MMK molecules, which fall in the same class of MM1, had a significant antihypertensive (40-80% compared to the drug losartan) activity. However, in vitro affinity studies showed that losartan has considerably higher affinity. The theoretical docking studies showed that MM1 acts on the same site of the receptor as losartan. They exert hydrophobic interactions with amino acid Val108 of the third helix of the AT1 receptor and other hydrophobic amino acids in spatial vicinity. In addition, losartan favours multiple hydrogen bondings between its tetrazole group with Lys199. These additional interactions may in part explain its higher in vitro binding affinity.
Design and synthesis of novel antihypertensive drugs
Moutevelis-Minakakis,Gianni,Stougiannou,Zoumpoulakis,Zoga,Vlahakos,Iliodromitis,Mavromoustakos
, p. 1737 - 1740 (2007/10/03)
AT1 antagonists constitute a new generation of drugs for the treatment of hypertension and are designed and synthesized to mimic the C-terminal segment of Angiotensin II (Ang II) and to block its binding action on AT1 receptor. For this reason, the conformational analysis of Ang II and its derivatives as well as the AT1 antagonists belonging to SARTANs class of molecules were studied. Such studies offer the possibility to reveal the stereoelectronic factors responsible for bioactivity of AT1 antagonists and to design and synthesize new analogues with better pharmacological and financial profiles. An example of a novel synthetic non-peptide molecule is given which mimics the His6-Pro7-Phe8 part of Ang II and is based on the (S)-pyroglutamic acid.
