194795-20-5

Upstream product

• 67-56-1 methanol 
• 709-16-0 2-hydroxy-phenylalanine 

Downstream Products

• 179187-31-6 methyl 2-((tert-butoxy)-carbonylamino)-3-(2-hydroxyphenyl)propanoate 
• 669062-37-7 methyl 2-((tert-butyloxycarbonyl)amino)-3-(2-(2-propen-1-yloxy)phenyl)propanoate 
• 669062-17-3 methyl N-(3-(chloromethyl)benzoyl)-2-(-2-propen-1-yloxy)phenylalaninate 
• 669062-19-5 methyl N-(3-(N-(2-propyn-1-yl)(4-iodophenyl)sulfonamidomethyl)benzoyl)(2-(2-propen-1-yloxy)phenyl)alaninate 
• 669062-08-2 methyl 18-((4-iodophenyl)sulfonyl)-16-methylidene-2-oxo-12-oxa-3,18-diazatricyclo[18.3.1.0^6,11]tetraeicosa-1⁽²⁴⁾,6,8,10,14,20,22-heptaene-4-carboxylate 
• 669062-28-6 18-((4-iodophenyl)sulfonyl)-16-methylidene-2-oxo-12-oxa-3,18-diazatricyclo[18.3.1.0^6,11]tetraeicosa-1⁽²⁴⁾,6,8,10,14,20,22-heptaene-4-carboxylic acid 
• 1263819-71-1 N-[6-(N-chlorambucilamino)hexanoyl]-DL-o-tyrosine methyl ester 
• 1263819-77-7 N-[6-(N-chlorambucilamino)hexanoyl]-DL-o-tyrosinol 
• 1263819-73-3 N-[11-(N-chlorambucilamino)undecanoyl]-DL-o-tyrosine methyl ester 
• 1263819-82-4 N-[11-(N-chlorambucilamino)undecanoyl]-DL-o-tyrosinol 

Relevant academic research and scientific papers

Discovery of a series of ester-substituted NLRP3 inflammasome inhibitors

The NLRP3 inflammasome is a component of the innate immune system involved in the production of proinflammatory cytokines. Aberrant activation by a wide range of exogenous and endogenous signals can lead to chronic, low-grade inflammation. It has attracted a great deal of interest as a drug target due to the association with diseases of large unmet medical need such as Alzheimer's disease, Parkinson's disease, arthritis, and cancer. To date, no drugs specifically targeting inhibition of the NLRP3 inflammasome have been approved. In this work, we used the known NLRP3 inflammasome inhibitor CP-456,773 (aka CRID3 or MCC 950) as our starting point and undertook a Structure-Activity Relationship (SAR) analysis and subsequent scaffold-hopping exercise. This resulted in the rational design of a series of novel ester-substituted urea compounds that are highly potent and selective NLRP3 inflammasome inhibitors, as exemplified by compounds 44 and 45. It is hypothesized that the ester moiety acts as a highly permeable delivery vehicle and is subsequently hydrolyzed to the carboxylic acid active species by carboxylesterase enzymes. These molecules are greatly differentiated from the state-of-the-art and offer potential in the treatment of NLRP3-driven diseases, particularly where tissue penetration is required.

CHEMICAL COMPOUNDS

The present disclosure relates to compounds of Formula (I): and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein inhibit the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as inter alia autoinflammatory and autoimmune diseases and cancers.

SAR study of tyrosine-chlorambucil hybrid regioisomers; Synthesis and biological evaluation against breast cancer cell lines

Amino acids were transformed and coupled to chlorambucil, a well-known chemotherapeutic agent, in an attempt to create new anticancer drugs with selectivity for breast cancer cells. Among the amino acids available, tyrosine was selected to act as an estrogenic ligand. It is hypothesized that tyrosine, which shows some structural similitude with estradiol, could possibly mimic the natural hormone and, subsequently, bind to the estrogen receptor. In this exploratory study, several tyrosine-drug conjugates have been designed. Thus, ortho-, meta-and para-tyrosine-chlorambucil analogs were synthesized in order to generate new anticancer drugs with structural diversity, more specifically in regards to the phenol group location. These new analogs were produced in good yield following efficient synthetic methodology. All the tyrosine-chlorambucil hybrids were more effective than the parent drug, chlorambucil. In vitro biological evaluation on estrogen receptor positive and estrogen receptor negative (ER and ER-) breast cancer cell lines revealed an enhanced cytotoxic activity for compounds with the phenol function located at position meta. Molecular docking calculations were performed for the pure L-ortho, L-meta-and L-paratyrosine phenolic regioisomers. The synthesis of all tyrosine-chlorambucil hybrid regioisomers and their biological activity are reported herein. Possible orientations within the targeted protein [estrogen receptor alpha (ERa)] are discussed in relation to the biological activity. Springer-Verlag 2011.

ANTICANCER AGENTS BASED ON AMINO ACID DERIVATIVES

The present invention provides compounds of formula (I): in which T is L or -A-NH-C(O)-L-; L is -(CH2)n- or -(CH2)p-Z-; A is -(CH2)m- or an alkyl component of a naturally occurring amino acid; R is -CO2R1, -CH2OH, -C(O)NH(hydroxyphenyl) or C(S)NH(hydroxyphenyl); R1 is H or is C1-C12 alkyl; X is -OH, OSO2R2, -Cl, -Br, or -I; R2 is C1-C12 alkyl or -CF3; Z is phenyl or naphthyl; m is an integer having a value of 1 to 20; n is an integer having a value of 1 to 20; and p is an integer having a value of 1 to 20 or an enantiomer, diastereoisomer, racemic mixture, pharmaceutically acceptable salt, solvate or prodrug thereof. These compounds can be useful as anticancer agents.

Synthesis of Diverse Macrocyclic Peptidomimetics Utilizing Ring-Closing Metathesis and Solid-Phase Synthesis

The synthesis of a range of highly functionalized peptidomimetic macrocycles has been accomplished using ring-closing metathesis and enyne tandem cross-metathesis-ring-closing metathesis reactions. This approach gives access to rigidified macrocycles mode

LTB4 antagonists and radiopharmaceuticals for imaging infection and inflammation

The present invention provides novel radiopharmaceutials useful for the diagnosis of infection and inflammation, reagents and kits useful for preparing the radiopharmaceuticals, methods of imaging sites of infection and/or inflammation in a patient, and methods of diagnosing diseases associated with infection or inflammation in patients in need of such diagnosis. The radiopharmaceuticals bind in vivo to the leukotriene B4 (LTB4) receptor on the surface of leukocytes which accumulate at the site of infection and inflammation. The reagents provided by this invention are also useful for the treatment of diseases associated with infection and inflammation.

Simultaneous dual isotope imaging of cardiac perfusion and cardiac inflammation

The present invention provides novel diagnostic compositions comprising a radiolabeled LTB4 binding agent and a radiolabeled perfusion imaging agent, diagnostic kits comprising such compositions, and methods of concurrent imaging in a mammal comprising ad

Radiopharmaceuticals for imaging infection and inflammation

The present invention provides novel radiopharmaceuticals useful for the diagnosis of infection and inflammation, reagents and kits useful for preparing the radiopharmaceuticals, methods of imaging sites of infection and/or inflammation in a patient, and

Radiopharmaceuticals for imaging infection and inflammation

The present invention provides novel radiopharmaceuticals useful for the diagnosis of infection and inflammation, reagents and kits useful for preparing the radiopharmaceuticals, methods of imaging sites of infection and/or inflammation in a patient, and