6245-91-6Relevant academic research and scientific papers
Screening of NOS activity and selectivity of newly synthesized acetamidines using RP-HPLC
Fantacuzzi, Marialuigia,Maccallini, Cristina,Di Matteo, Mauro,Ammazzalorso, Alessandra,Bruno, Isabella,De Filippis, Barbara,Giampietro, Letizia,Mollica, Adriano,Amoroso, Rosa
, p. 419 - 424 (2016/02/16)
Nitric Oxide Synthase (NOS) inhibitors could play a powerful role in inflammatory and neurodegenerative diseases. In this work, novel acetamidine derivatives of NOS were synthesized and the inhibitor activity was evalued. To screen the activity and selectivity, the l-citrulline residue, after the enzymatic NOS assay, was derivatized with o-phthaldialdehyde/N-acetyl cysteine (OPA/NAC) and then evaluated by RP-HPLC method with fluorescence detection.All compounds did not affect the activity of endothelial and neuronal isoforms, while nine of them possessed a percentage of iNOS activity at 10 μM lower than 50%, and were selected for IC50 evaluation. Among them, a compound emerged as a very potent (IC50 of 53 nM) and selective iNOS inhibitor.
Studies toward the discovery of the next generation of antidepressants. 3. Dual 5-HT1A and serotonin transporter affinity within a class of N-aryloxyethylindolylalkylamines
Mewshaw, Richard E.,Zhou, Dahui,Zhou, Ping,Shi, Xiaojie,Hornby, Geoffrey,Spangler, Taylor,Scerni, Rosemary,Smith, Deborah,Schechter, Lee E.,Andree, Terrance H.
, p. 3823 - 3842 (2007/10/03)
N-Aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT1A affinity are described. These compounds represent truncated analogues of our previously reported piperidinyl derivatives (3). Compounds in this investigation were found to have more similar affinities and functional activities for the 5-HT1A receptor and 5-HT transporter. Though 5-HT1A antagonism is not consistently observed throughout series 5, several molecular features were found to be essential to obtain high and balanced activities. The proper placement of a heteroatom in the aryl ring and the length of the linkage used to tether the indole moiety had significant influence on 5-HT1A and 5-HT transporter affinities. Introduction of a halogen into the aryl ring usually lowered intrinsic activity and in some cases led to full 5-HT1A antagonists. Compounds 33 and 34 were observed to be full 5-HT1A antagonists with Ki values of approximately 30 nM for the 5-HT1A receptor and Ki values of 5 and 0.5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the α1 receptor.
Intramolecular Mannich reaction of 2-oxotryptamine and homologues with oxo reagents yielding spiro compounds. Part II
Doernyei, Gabor,Incze, Maria,Kajtar-Peredy, Maria,Szantay, Csaba
, p. 1669 - 1680 (2007/10/03)
2-Oxotryptamine and its homo derivative undergo intramolecular Mannich-type cyclization with acetone and other ketones to give spiro[indole-3,3′-pyrrolidin]-2-ones and spiro[indole-3,3′-piperidin]-2-ones. A similar reaction with the bis-homologue of 2-oxotryptamine to yield spiro[azepane-3,3′-indol]-2′-ones was unsuccessful.
A GENERAL METHOD FOR THE SYNTHESIS OF INDOLES BEARING A VARIETY OF SUBSTITUENTS AT THE β-POSITION, AND ITS APPLICATION TO THE SYNTHESIS OF L-TRYPTOPHAN
Shono, Tatsuya,Matsumura, Yoshihiro,Kanazawa, Takenobu
, p. 1259 - 1262 (2007/10/02)
A general synthetic method of β-substituted indoles such as indolacetic acid, tryptamine and L-tryptophan has been exploited utilizing α-methoxylated amides, lactams, a carbamate, and sulfonamides, easily obtainable by an electrochemical method, as key intemediates.
Cardiac-Slowing Amidines Containing the 3-Thioindole Group. Potential Antianginal Agents
Zelesko, Michael J.,McComsey, David F.,Hageman, William E.,Nortey, Samuel O.,Baker, Carol A.,Maryanoff, Bruce E.
, p. 230 - 237 (2007/10/02)
A series of 3-thioindolamidines (and 3-indolamidines) related to mixidine (1) was studied for cardiac-slowing properties, allowing the discovery of activity for prototype thioindole 2.Structure-activity relationships were explored, leading to many potent antitachycardic agents (6-9, 12, 13, 15-17, 20, 23, 24, 30, 34, 35, 45, and 47-49).Relative to 2, cardiac-slowing activity is enhanced by substitution of the indole nitrogen with small (C1-C3) saturated alkyl groups (6-9), unsaturated alkyl groups (12, 13, and 15-17), or a methoxyethyl group (20); replacement of the N-methyl group with alkyl (23) or phenyl groups (24); and extension of the ethylene bridge by two methylene units (34).Dethio (i.e., 3-indole) analogues of 2 with alkyl substitution on the indole nitrogen (47-49) have greater activity as well.Several potent compounds were also found to have minimal myocardial depression (6-9, 13, 45, and 47).Secondary pharmacological testing is reported for thioindoles 2, 6, 7, 9, and 28.
