32324-23-5Relevant academic research and scientific papers
Design, Synthesis, and Biological Evaluation of Novel, Non-Brain-Penetrant, Hybrid Cannabinoid CB1R Inverse Agonist/Inducible Nitric Oxide Synthase (iNOS) Inhibitors for the Treatment of Liver Fibrosis
Iyer, Malliga R.,Cinar, Resat,Katz, Alexis,Gao, Michael,Erdelyi, Katalin,Jourdan, Tony,Coffey, Nathan J.,Pacher, Pal,Kunos, George
, p. 1126 - 1141 (2017/02/19)
We report the design, synthesis, and structure-activity relationships of novel dual-target compounds with antagonist/inverse agonist activity at cannabinoid receptor type 1 (CB1R) and inhibitory effect on inducible nitric oxide synthase (iNOS). A series of 3,4-diarylpyrazolinecarboximidamides were synthesized and evaluated in CB1 receptor (CB1R) binding assays and iNOS activity assays. The novel compounds, designed to have limited brain penetrance, elicited potent in vitro CB1R antagonist activities and iNOS inhibitory activities. Some key compounds displayed high CB1R binding affinities. Compound 7 demonstrated potent in vivo pharmacological activities such as reduction of food intake mediated by the antagonism of the CB1Rs and antifibrotic effect in the animal models of fibrosis mediated by iNOS inhibition and CB1R antagonism.
Convenient synthesis of structurally novel 1,3-disubstituted azetidine derivatives
Kharul, Rajendra K.,Goswami, Amitgiri,Gite, Archana,Godha, Atul K.,Jain, Mukul,Patel, Pankaj R.
, p. 1703 - 1717 (2008/09/20)
A convenient synthesis of structurally novel 1,3-disubstituted azetidine derivatives is described. The approach involves condensation of an azetidine building block with sulfonylated carbamic acid methyl ester, subsequently followed by quenching the imidoyl chloride with amines. Different derivatives were prepared by substituting benzhydrol as well as benzenesulfonamide as part of the core structure. Copyright Taylor & Francis Group, LLC.
Inhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold
Groutas, William C,He, Shu,Kuang, Rongze,Ruan, Sumei,Tu, Juan,Chan, Ho-Kit
, p. 1543 - 1548 (2007/10/03)
A challenge associated with drug design is the development of selective inhibitors of proteases (serine or cysteine) that exhibit the same primary substrate specificty, that is, show a preference for the same P1 residue. While these proteases have similar active sites, nevertheless there are subtle differences in their S and S' subsites which can be exploited. We describe herein for the first time the use of functionalized sulfonamides as a design and diversity element which, when coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold yields potent, time-dependent inhibitors of the serine proteases human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G(Cat G). Our preliminary findings suggest that (a) appending to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold recognition and diversity elements that interact with both S and S' subsites of a target protease may result in optimal enzyme selectivity and potency and, (b) functionalized sulfonamides constitute a powerful design and diversity element with low intrinsic chemical reactivity and potentially wide applicability. Copyright
Mild and Efficient Synthesis of Aromatic Sulfonamides by in situ Preparation of the Corresponding Sulfonyl Isothiocyanates
Arnswald, Martin,Neumann, Wilhelm P.
, p. 1997 - 2000 (2007/10/02)
A new reaction between chlorosulfonyl isocyanate (1) and trialkylstannyl-substituted arenes 2a-k, 7, 9 is described.It provides the aromatic sulfonyl isocyanates 3 or their derivatives, the sulfonamides 4a-j, the sulfonylcarbamates 5a-b, or sulfonylureas 6, respectively.The trialkylstannyl group as an efficient leaving group allows mild reaction conditions to be applied and unusual substitution patterns to be obtained, normally not accessible by electrophilic aromatic substitutions.Thus, sulfonamidation can be achieved in meta position to a trifluoromethyl group. Key words: Electrophilic aromatic substitution; sulfodestannalytion; isocyanates, sulfonyl, aromatic; sulfonyl compounds; trialkylarylstannanes, application of
