36397-23-6Relevant academic research and scientific papers
Compound 48/80. Structure activity relations and poly THIQ, a new, more potent analog
Read,Kiefer,Weber
, p. 1292 - 1295 (1973)
Derivatives of p methoxyphenethylmethylamine were synthesized from which formaldehyde copolymers analogous to compound 48/80 were prepared. Measurement of the hypotensive activity of these analogs revealed that potency was not enhanced by changing the group in the para position, by varying the length of the alkyl group, or by altering the degree of methylation of the amine. However, when the ethylamine side chain was cyclized to form 7 methoxytetrahydroisoquinoline, the copolymer prepared from this derivative (poly THIQ) was seven times more potent than compound 48/80. The hypotensive action of poly THIQ was found to result from the liberation of histamine, as with compound 48/80.
Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists
Yi, Ce,Xing, Gang,Wang, Siqi,Li, Xiaoran,Liu, Yichuang,Li, Jinyan,Lin, Bin,Woo, Anthony Yiu-Ho,Zhang, Yuyang,Pan, Li,Cheng, Maosheng
, (2019/11/26)
A series of β2-adrenoceptor agonists with an 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one moiety is presented. The stimulatory effects of the compounds on human β2-adrenoceptor and β1-adrenoceptor were characterized by a cell-based assay. Their smooth muscle relaxant activities were tested on isolated guinea pig trachea. Most of the compounds were found to be potent and selective agonists of the β2-adrenoceptor. One of the compounds, (R)-18c, possessed a strong β2-adrenoceptor agonistic effect with an EC50 value of 24 pM. It produced a full and potent airway smooth muscle relaxant effect same as olodaterol. Its onset of action was 3.5 min and its duration of action was more than 12 h in an in vitro guinea pig trachea model of bronchodilation. These results suggest that (R)-18c is a potential candidate for long-acting β2-AR agonists.
Fast Titanium-Catalyzed Hydroaminomethylation of Alkenes and the Formal Conversion of Methylamine
Bielefeld, Jens,Doye, Sven
supporting information, p. 6138 - 6143 (2020/03/13)
The scientific interest in catalytic hydroaminoalkylation reactions of alkenes has vastly increased over the past decade, but these reactions have struggled to become a viable option for general laboratory or industrial use because of reaction times of several days. The titanium-based catalytic system introduced in this work not only reduces the reaction time by several orders of magnitude, into the range of minutes, but the catalyst is also demonstrated to be easily available from common starting materials, at a cost of approximately 1 € per millimole of catalyst. We were also able to formally perform C?H activation of methylamine and achieve coupling to a broad variety of alkenes, through silyl protection of the amine and simple deprotection by water.
Synthesis of Potent and Selective Inhibitors of Aldo-Keto Reductase 1B10 and Their Efficacy against Proliferation, Metastasis, and Cisplatin Resistance of Lung Cancer Cells
Endo, Satoshi,Xia, Shuang,Suyama, Miho,Morikawa, Yoshifumi,Oguri, Hiroaki,Hu, Dawei,Ao, Yoshinori,Takahara, Satoyuki,Horino, Yoshikazu,Hayakawa, Yoshihiro,Watanabe, Yurie,Gouda, Hiroaki,Hara, Akira,Kuwata, Kazuo,Toyooka, Naoki,Matsunaga, Toshiyuki,Ikari, Akira
, p. 8441 - 8455 (2017/11/03)
Aldo-keto reductase 1B10 (AKR1B10) is overexpressed in several extraintestinal cancers, particularly in non-small-cell lung cancer, where AKR1B10 is a potential diagnostic marker and therapeutic target. Selective AKR1B10 inhibitors are required because compounds should not inhibit the highly related aldose reductase that is involved in monosaccharide and prostaglandin metabolism. Currently, 7-hydroxy-2-(4-methoxyphenylimino)-2H-chromene-3-carboxylic acid benzylamide (HMPC) is known to be the most potent competitive inhibitor of AKR1B10, but it is nonselective. In this study, derivatives of HMPC were synthesized by removing the 4-methoxyphenylimino moiety and replacing the benzylamide with phenylpropylamide. Among them, 4c and 4e showed higher AKR1B10 inhibitory potency (IC50 4.2 and 3.5 nM, respectively) and selectivity than HMPC. The treatments with the two compounds significantly suppressed not only migration, proliferation, and metastasis of lung cancer A549 cells but also metastatic and invasive potentials of cisplatin-resistant A549 cells.
Efficient conversion of primary and secondary alcohols to primary amines
Sun, Weilin,Pelletier, Jeffrey C.
, p. 7745 - 7746 (2008/02/12)
A convenient single-vessel conversion of primary and secondary alcohols to primary amines is reported. Use of this method results in substantially cleaner crude products than similar procedures reported in the literature. A simple work-up also makes this procedure ideal for parallel synthesis.
Novel selective inhibitors of neutral endopeptidase for the treatment of female sexual arousal disorder
Pryde, David C.,Cook, Andrew S.,Burring, Denise J.,Jones, Lyn H.,Foll, Stephanie,Platts, Michelle Y.,Sanderson, Vivienne,Corless, Martin,Stobie, Alan,Middleton, Donald S.,Foster, Laura,Barker, Laura,Van Der Graaf, Piet,Stacey, Peter,Kohl, Christopher,Coggon, Sara,Beaumont, Kevin
, p. 142 - 159 (2007/10/03)
A series of substituted glutaramides were synthesised using Candoxatrilat 1 as a lead and evaluated for potency against neutral endopeptidase (NEP) as a potential treatment for female sexual arousal disorder (FSAD). In this paper, we describe studies in which we were able to increase NEP activity substantially over the levels reported for previous compounds from this programme by appropriate substitution in both the P1′ and P2′ regions. Optimisation led to the 4-chlorophenpropylamide S-30 which was selected as a candidate for further study.
Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: Drugs for cystic fibrosis and chronic bronchitis
Hirsh, Andrew J.,Molino, Bruce F.,Zhang, Jianzhong,Astakhova, Nadezhda,Geiss, William B.,Sargent, Bruce J.,Swenson, Brian D.,Usyatinsky, Alexander,Wyle, Michael J.,Boucher, Richard C.,Smith, Rick T.,Zamurs, Andra,Johnson, M. Ross
, p. 4098 - 4115 (2007/10/03)
Amiloride (1), the prototypical epithelial sodium channel (ENaC) blocker, has been administered with limited success as aerosol therapy for improving pulmonary function in patients with the genetic disorder cystic fibrosis. This study was conducted to synthesize and identify more potent, less reversible ENaC blockers, targeted for aerosol therapy and possessing minimal systemic renal activity. A series of novel 2-substituted acylguanidine analogues of amiloride were synthesized and evaluated for potency and reversibility on bronchial ENaC. All compounds tested were more potent and less reversible at blocking sodium-dependent short-circuit current than amiloride. Compounds 30-34 showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found (compounds 30, 39, and 40), whereas no stereospecific (compounds 33, 34) difference in potency on ENaC was displayed. Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloríde and displayed the lowest IC50 value ever reported for an ENaC blocker.
Investigation into the structure-activity relationship of novel concentration dependent, dual action T-type calcium channel agonists/antagonists
McCalmont, William F.,Patterson, Jaclyn R.,Lindenmuth, Michael A.,Heady, Tiffany N.,Haverstick, Doris M.,Gray, Lloyd S.,Macdonald, Timothy L.
, p. 3821 - 3839 (2007/10/03)
This paper describes the synthesis and biological evaluation of a series of straight chain analogs of a compound (1) that was previously synthesized in our research program. These compounds, which are T-type calcium channel antagonists, exhibits potent anti-proliferative activity against a variety of cancer cells. A structure-activity relationship of these analogs against a variety of cancer cells has provided insight into a logical pharmacophore for this series of compounds. Furthermore, this series of compounds has presented itself as a set of novel, concentration dependent, dual action agonists/antagonists for the T-type calcium channel.
N-phenpropylcuclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
-
, (2008/06/13)
The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R1 is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C1-6alkoxy, —NR2 R3 or —NR4SO2R5; X is the linkage —(CH2)n— or —(CH2)q—O— (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy; hydroxy; hydroxy(C1-3alkyl); C3-7cycloalkyl; carbocyclyl; heterocyclyl; or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6 or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5- or 6-membered carbocyclic or heterocyclyic ring.
Sodium channel blockers
-
, (2008/06/13)
The present invention relates to sodium channel blockers. The present invention also relates to a variety of methods of treatment using these sodium channel blockers.
