39544-74-6

Usage

Uses

Used in Pharmaceutical Industry:
BENZOTRIPT is used as a receptor antagonist for the treatment of conditions related to the cholecystokinin receptor. Its application reason is to modulate the interaction between cholecystokinin and its receptor, potentially leading to therapeutic benefits in various conditions.
BENZOTRIPT is also used as an analgesic enhancer in combination with morphine for the management of pain. The application reason is its ability to potentiate the effects of morphine by interacting with opioid receptors, which can result in improved pain relief and potentially reduced morphine dosage requirements.

References

1) Hahne (1981), Proglumide and benzotript: Members of a different class of cholecystokinin receptor antagonists; Proc. Natl. Acad. Sci. USA. 78 6304 2) Gaudreau et al. (1990), Cholecystokinin antagonists proglumide, lorglumide and benzotript, but not L-364,718, interact with brain opioid binding sites; Neuropeptides 16 51

InChI:InChI=1/C18H15ClN2O3/c19-13-7-5-11(6-8-13)17(22)21-16(18(23)24)9-12-10-20-15-4-2-1-3-14(12)15/h1-8,10,16,20H,9H2,(H,21,22)(H,23,24)/p-1/t16-/m1/s1

Upstream product

• 74-11-3 para-chlorobenzoic acid 
• 122-01-0 4-chloro-benzoyl chloride 
• 73-22-3 L-Tryptophan 

Downstream Products

• 1435265-14-7 N-(N-4-chlorobenzoyl-L-tryptophanyl)-D-phenylalanine methyl ester 
• 95579-05-8 (S)-2-(4-Chloro-benzoylamino)-3-(2-oxo-2,3-dihydro-1H-indol-3-yl)-propionic acid 

Relevant academic research and scientific papers

Mercaptoacetate thioesters and their hydrolysate mercaptoacetic acids jointly inhibit metallo-β-lactamase L1

The 'superbug' infection caused by metallo-β-lactamases (MβLs) including L1 has grown into an emerging threat. To probe whether mercaptoacetate thioesters inhibiting L1 is a contribution of the thioester itself or its hydrolysate, ten mercaptoacetate thioesters 1-10 were synthesized, which specifically inhibited L1, exhibiting IC50 values ranging from 0.17 to 1.2 μM, and 8 was found to be the best inhibitor (IC50 = 0.17 μM). These thioesters restored the antimicrobial activity of cefazolin against E. coli expressing L1 by 2-4-fold. UV-vis monitoring showed that 1, 8 and 9 were unhydrolyzed in Tris buffer (pH 6.0-8.5), but hydrolyzed by L1; further HPLC monitoring indicated that 1/3 of the thioester 9 was converted to mercaptoacetic acid. STD-NMR monitoring suggested that both the thioester and its hydrolysate mercaptoacetic acid jointly inhibited L1.

Design and synthesis of tryptophan containing dipeptide derivatives as formyl peptide receptor 1 antagonist

Our previous studies identified an Fmoc-(S,R)-tryptophan-containing dipeptide derivative, 1, which selectively inhibited neutrophil elastase release induced by formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) in human neutrophils. In an attempt to improve pharmacological activity, a series of tryptophan-containing dipeptides were synthesized and their pharmacological activities were investigated in human neutrophils. Of these, five compounds 3, 6, 19a, 24a, and 24b exhibited potent and dual inhibitory effects on FMLP-induced superoxide anion (O2-) generation and neutrophil elastase release in neutrophils with IC50 values of 0.23/0.60, 1.88/2.47, 1.87/3.60, 0.12/0.37, and 1.32/1.03 μM, respectively. Further studies indicated that inhibition of superoxide production in human neutrophils by these dipeptides was associated with the selective inhibition of formyl peptide receptor 1 (FPR1). Furthermore, the results of structure-activity relationship studies concluded that the fragment N-benzoyl-Trp-Phe-OMe (3) was most suitable as a core structure for interaction with FPR1, and may be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases. As some of the synthesized compounds exhibited separable conformational isomers, and showed diverse bioactivities, the conformation analysis of these compounds is also discussed herein. The Royal Society of Chemistry 2013.

N-Benzoyl amino acids as ICAM/LFA-1 inhibitors. Part 2: Structure-activity relationship of the benzoyl moiety

o-Bromobenzoyl L-tryptophan 1 inhibits the association of LFA-1 with ICAM-1 with an IC50 of 1.7μM. Evaluation of the structure-activity relationship of the benzoyl moiety shows that 2,6-di-substitutions greatly enhance potency of this class of inhibitors. Electronegative substitutions that favor a 90°angle between the benzoyl ring and the amide bond yield the most potent compounds. There is a strong correlation between the potency of the compounds and the difference between the ab initio energy at 90°and the global minima energy for given compounds. Combining the favored benzoyl substitutions with L-histidine and L-asparagine resulted in a 15-fold increase in potency over compound 1.

CCK antagonists

In general, the invention features CCK antagonist compounds having the formula: STR1 or a pharmaceutically acceptable salt thereof, wherein each R1 is, independently, an alkyl group having 1 to 5, inclusive, carbon atoms, an alkoxy group having 1 to 5, inclusive, carbon atoms, a halogen, amino, hydroxy, nitro, cyano, carboxyl, trifluoromethyl, ethyl carboxylate, or a hydrogen; m is an integer between 0 and 2, inclusive; and A is either STR2 where n is an integer between 1 and 5, inclusive, and R2 is hydroxy, an alkoxy group having 1 to 5, inclusive, carbon atoms, aralkoxy (e.g., benzyloxy), aralkyl (e.g., benzyl), amino, an alkyl group having 1 to 5, inclusive, carbon atoms, an alkylamino group having 1 to 5, inclusive, carbon atoms, a dialkylamino group with each alkyl group, independently having 1 to 5, inclusive, carbon atoms, a cycloalkylamino group wherein the ring has 4 to 6, inclusive, carbon atoms (e.g., pyrrolidino, piperidino, N-methylpiperazino), or morpholino; or A is an alkyl group having 1 to 5, inclusive, carbon atoms, a hydroxyalkyl group having 1 to 5, inclusive, carbon atoms, an alkoxyalkyl group having 2 to 8, inclusive, carbon atoms, an aralkoxyalkyl having 8 to 14, inclusive, carbon atoms, in aryl group (e.g., phenyl, toluyl) having 6 to 14, inclusive, carbon atoms, an aralkyl group (e.g., benzyl, phenylethyl)having 6 to 14, inclusive, carbon atoms, and a cycloalkyl group having 3 to 12, inclusive, carbon atoms.

N-p-chlorobenzoyl tryptophane, salts and compositions thereof

Pharmaceutically active L-tryptophane compounds comprising the compound of the formula: STR1 AND ITS CALCIUM, MAGNESIUM AND ALUMINUM SALTS. These compounds exhibit superior pharmacologic activity on the gastroenteric tract.