85753-12-4

Upstream product

• 21691-50-9 Ala-OtBu 
• 100-52-7 benzaldehyde 
• 13404-22-3 tert-butyl L-alaninate hydrochloride 
• 100-39-0 benzyl bromide 

Downstream Products

• 256477-48-2 N-benzyl-N-[(1,4-dichloro-7-isoquinolinyl)sulphonyl]-L-alanine tert-butyl ester 
• 7585-47-9 N-benzyl-(S)-alanine 
• 344765-29-3 1-benzyl-4-tert-butoxycarbonyl-4-methyl-2-azetidinone 
• 344765-41-9 1-benzyl-4-carboxy-4-methyl-2-azetidinone 
• 256478-37-2 N-benzy-N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-L-alanine tert-butyl ester 
• 344765-16-8 N-benzyl-N-chloroacetyl-L-Ala-O^tBu 

Relevant academic research and scientific papers

Structure-Activity Relationship Studies of Hydantoin-Cored Ligands for Smoothened Receptor

An underside binding site was recently identified in the transmembrane domain of smoothened receptor (SMO). Herein, we report efforts in the exploration of new insights into the interactions between the ligand and SMO. The hydantoin core in the middle of the parent compound was found to be highly conservative in chirality, ring size, and substituents. On each benzene at two ends, a plethora of variations, particularly halogen substitutions, were introduced and investigated. Analysis of the structure-activity relationship revealed miscellaneous halogen effects. The ligands with double halogen substituents exhibit remarkably enhanced potency, providing promising candidates that potentially overcome the common drug resistance and useful heavy-atom labeled chemical tools for co-crystallization studies of SMO.

Colocalization Strategy Unveils an Underside Binding Site in the Transmembrane Domain of Smoothened Receptor

We unveiled an underside binding site on smoothened receptor (SMO) by a colocalization strategy using two structurally complementary photoaffinity probes derived from a known ligand Allo-1. Docking study and structural dissection identified key interactions within the site, including hydrogen bonding, πinteractions, and hydrophobic interactions between Allo-1 and its contacting residues. Taken together, our results reveal the molecular base of Allo-1 binding and provide a basis for the design of new-generation ligands to overcome drug resistance.

Structure-Activity Relationships of the Peptide Kappa Opioid Receptor Antagonist Zyklophin

The dynorphin (Dyn) A analogue zyklophin ([N-benzyl-Tyr1-cyclo(d-Asp5,Dap8)]dynorphin A(1-11)NH2) is a kappa opioid receptor (KOR)-selective antagonist in vitro, is active in vivo, and antagonizes KOR in the CNS

ABIRATERONE DERIVATIVES AND NON-COVALENT COMPLEXES WITH ALBUMIN

The present disclosure provides derivatives of abiraterone, non-covalently bound complexes of the abiraterone derivatives with serum albumin, pharmaceutical compositions of the same, and methods of use thereof. The non-covalently bound complexes are significantly more water-soluble than abiraterone and are useful for the treatment of a disease or condition that can benefit from CYP17 inhibition, such as prostate cancer.

Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines

1-Isoquinolinylguanidines were previously disclosed as potent and selective inhibitors of urokinase-type plasminogen activator (uPA). Further investigation of this template has revealed that incorporation of a 7-sulfonamide group furnishes a new series of potent and highly selective uPA inhibitors. Potency and selectivity can be achieved with sulfonamides derived from a variety of amines and is further enhanced by the incorporation of sulfonamides derived from amino acids. The binding mode of these 1-isoquinolinylguanidines has been investigated by X-ray cocrystallization studies. uPA inhibitor 26 was selected for further evaluation based on its excellent enzyme potency (Ki 10 nM) and selectivity profile (4000-fold versus tPA and 2700-fold versus plasmin). In vitro, compound 26 is able to inhibit exogenous uPA in human chronic wound fluid (IC50 = 0.89 μM). In vivo, in a porcine acute excisional wound model, following topical delivery, compound 26 is able to penetrate into pig wounds and inhibit exogenous uPA activity with no adverse effect on wound healing parameters. On the basis of this profile, compound 26 (UK-371,804) was selected as a candidate for further preclinical evaluation for the treatment of chronic dermal ulcers.

Composition for the treatment of damaged tissue

A pharmaceutical for use in damaged tissue, such as wound, treatment (e.g. healing) is described. The pharmaceutical comprising a composition which comprises: (a) a growth factor; and (b) an inhibitor agent; and optionally (c) a pharmaceutically acceptable carrier, diluent or excipient; wherein the inhibitor agent can inhibit the action of at least one specific adverse protein (e.g. a specific protease) that is upregulated in a damaged tissue, such as a wound, environment.