2853-29-4Relevant articles and documents
Teaching an old scaffold new recognition tricks: Oligopyrrolamide antagonists of IAPP aggregation
Kumar, Sunil,Vogel, Maria C.,Hamilton, Andrew D.
supporting information, p. 733 - 741 (2018/02/09)
A library of N-substituted oligopyrrolamides was designed to modulate the aggregation kinetics of islet amyloid polypeptide (IAPP). IAPP is a hormonal peptide, co-secreted with insulin in the pancreatic β-cells. IAPP samples a variety of conformations, starting from a native random coil to membrane-associated α-helical intermediates and eventually terminates in the amyloid plaques rich in β-sheet structures. A growing body of evidence suggests that membrane bound α-helical intermediates are the key cytotoxic species that impair the functionality and viability of β-cells and contribute to the onset of type 2 diabetes mellitus (DM2). The N-substituted oligopyrrolamides were screened against the aggregation of IAPP using amyloid kinetic assays. A tripyrrole, ADH-101, was the most effective antagonist of IAPP fibrillation in a physiologically relevant lipid membrane system as well as under de novo conditions. ADH-101 induces/stabilizes a secondary structure in IAPP which potentially affects its downstream functions. ADH-101 efficiently affects IAPP-mediated liposome leakage and cell toxicity in insulin secreting cells. ADH-101 inhibits the elongation process potentially binding to the monomeric IAPP and attenuating its access to the preformed fibers. More importantly, oligopyrrolamides are better inhibitors of IAPP aggregation than analogous oligopyridylamides and have more desirable biological properties reflected by their partition coefficients. In essence, an oligopyrrolamide scaffold has been designed which modulates the membrane bound helical intermediates of IAPP and affects their downstream functions such as oligomerization, membrane poration, and cytotoxicity.
Heterocyclylamide-substituted thiazoles, pyrroles and thiophenes
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Page/Page column 9, (2010/06/19)
The invention relates to heterocyclylamide-substituted thiazoles, pyrroles and thiophenes and to processes for preparing them, to their use for the treatment and/or prophylaxis of diseases, and to their use for the production of medicaments for the treatm
4-(Anilino)pyrrole-2-carboxamides: Novel non-steroidal/non-anilide type androgen antagonists effective upon human prostate tumor LNCaP cells with mutated nuclear androgen receptor
Wakabayashi, Ken-ichi,Imai, Keisuke,Miyachi, Hiroyuki,Hashimoto, Yuichi,Tanatani, Aya
, p. 6799 - 6812 (2008/12/22)
Various 4-(anilino)pyrrole-2-carboxamides were designed and synthesized as novel androgen receptor (AR) antagonists without steroidal or anilide structure, based on our strategy for developing full antagonists of nuclear receptors. Introduction of a bulky
Syntheses of substituted 1-methyl-2-(1,3,4-thiadiazol-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles
Firoozi,Javidnia,Kamali,Fooladi,Foroumadi,Shafiee
, p. 123 - 128 (2007/10/02)
Starting from readily available ethyl-4-nitropyrrole-2-carboxylate (1), substituted 1-methyl-2-(1,3,4-thiadiazel-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles were prepared. The reaction of 1 with diazemethane gave ethyl 1-methyl-4-nitropyrrole-2-carboxylate (2). Reaction of compound 2 with hydrazine hydrate afforded the corresponding hydrazide 3. The reaction of 3 with formic acid yielded 1-(1-methyl-4-nitropyrrole-2-carboxyl)-2-(formyl)hydrazine (7). Refluxing of the latter with phosphorus pentasulfide in xylene yielded compound 6 in 40% yield. Reaction of compound 7 with phosphorus pentoxide afforded compound 9. Reaction of compound 3 with 1,1'-carboxyldiimidazole in the presence of triethylamine yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-oxadiazoline-4(H)-5-one (11). Refluxing compound 3 with cyanogen bromide in methanol gave compound 12. Compound 13 could be obtained through the reaction of compound 3 with carbon disulfide in basic medium. Alkylation of compound 13 afforded the corresponding alkylthio derivative 14. Reaction of 1-methyl-4-nitropyrrole-2-carboxylic acid (15) with thiosemicarbazide and phosphorus oxychloride gave 2-amino-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole (16). Sandmeyer reaction of compound 16 yielded 2-chloro-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole (17). Refluxing of the latter with thiourea afforded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazotine-4(H)-5-thione (18). Alkylation of compound 18 gave the corresponding alkylthio derivative 19. Oxidation of the latter with hydrogen poroxide in acetic acid yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-5-methylsulfonyl-1,3,4-thiadiazole (20).
Synthesis of chiral NADH model compounds in the pyrrolo[3,2-b]pyridine series: Models with a chiral group on the pyrrole nitrogen or on the carboxamide side chain
Monnet,Prevost,Dupas,Bourguignon,Queguiner
, p. 5831 - 5844 (2007/10/02)
The synthesis of chiral NADH model compounds in the pyrrolo[3,2-b]pyridine series is described, using various strategies. The first route involved alkylation of the pyrrole nitrogen of a nitropyrrole carboxylate followed by a ring closure reaction in a [3
Hypolipidemic and antiatherosclerotic novel (monosubstituted-amino)heteroaryl carboxylic acids and analogs
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, (2008/06/13)
This disclosure described novel (monosubstituted-amino)heteroaryl carboxylic acids and analogs which are useful as hypolipidemic and antiatherosclerotic agents.
PREPARATIVE ASPECTS OF THE NITRATION OF 1-METHYLPYRROLE DERIVATIVES. 13C NMR OF SOME NITROPYRROLES.
Grehn
, p. 67 - 77 (2007/10/04)
The nitration of 1-methylpyrrole and 1,2-dimethylpyrrole was studied and the products were characterized. It was found that the nitration of ethyl 1-methylpyrrole-2-carboxylate depends on the reaction conditions. **1**3C parameters have been determined for several 1-methyl substituted pyrrole- and nitropyrrole derivatives and the relationship between the observed and predicted **1**3C shifts for aromatic carbons is briefly discussed. It has been found that the determination of the direct **1**3C-**1H coupling constants in the pyrrole ring constitutes a useful tool for distinguishing alpha - and beta -positions.
