66737-89-1

Upstream product

• 124-38-9 carbon dioxide 
• 14804-34-3 3-tert-butyl-4-methoxybromobenzene 
• 125182-27-6 methyl 3-tert-butyl-4-methoxybenzoate 

Downstream Products

• 142651-19-2 1-(3-(tert-butyl)-4-methoxyphenyl)ethan-1-one 
• 66737-88-0 4-hydroxy-3-tert-butyl benzoic acid 
• 171365-85-8 ethyl 4-<(E)-2-(3-tert-butyl-4-methoxyphenyl)propenyl>benzoate 

Relevant academic research and scientific papers

BICYCLIC COMPOUNDS USEFUL AS CATHEPSIN S INBHIBITORS

Compounds of formula (I), wherein R1, R2, R3, Ra and E are are defined within, and pharmaceutically acceptable salts, solvates, hydrates and N-oxides thereof having utility in the treatment of disorders mediated by cathepsin S.

CATHEPSIN S INHIBITORS

Compounds of the formula (I) where R1 is C1-C4 straight or branched alkyl, optionally substituted with up to three substituents selected from halo and hydroxy; R2 is halo, hydroxy, methyloxy, or C1-C2 alkyl, which alkyl is optionally substituted with up to three halogens or an hydroxy or a methyloxy; D is - C3-C7 alkylene-, thereby defining a cycloalkyl ring; E is -C(=O)-, -S(=O)m-, -NRdS(=O)m-, -NRaC(=O)-, -OC(=O)-, R3 is an optionally substituted carbocyclic or heterocyclic ring R10 is H, ORc, SRc or together with the gem H is =O or (ORc)2; Ra is independently selected from H, C1-C4 alkyl; have utility in the inhibition of cathepsin S and are thus useful pharmaceuticals against disorders such as autoimmune disorders and chronic pain.

Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity

The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma, multiple sclerosis, artherosclerosis, and rheumatoid arthritis.

Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes

The retinoic acid receptors (RARs) transduce retinoid dependant gene regulation, and many biological effects of retinoids are mediated through binding and activation of three closely related receptor subtypes (RARα, RARβ, and RARγ). In order to investigate the role of receptor subtypes, we have carried out a chemical synthesis program to seek selective retinoids for these receptors. We measured receptor binding affinity using recombinant RARα, -β, and -γ proteins and assessed cellular differentiating activity in F9 murine teratocarcinoma cells (F9 cells). This research has identified the 4-substituted-3-(1-adamantyl)phenyl moiety as a new pharmacophore which can replace the β-cyclogeranylidene ring of the naturally ocurring all- trans-retinoic acid. Two chemical series derived from the general structures 6-(3-tertioalkyl-phenyl)-2-naphthoic acid (series I) and 4-[(E)-2-(3- tertioalkylphenyl)propenyl]benzoic acid (series II) were developed. In particular, we have obtained the RARγ selective derivatives 6-[3-(1- adamantyl)-4-hydroxyphenyl]-2-naphthoic acid (7) [K(i)(RARα) = 6500 nM, Ki(RARβ) = 2480 nM, K(i)(RARγ) = 77 nM] and 4-[(E)-2-[3-(1-adamantyl)-4- hydroxyphenyl]propenyl]benzoic acid (19) [K(i)(RARα) = 1 144 nM, K(i)(RARβ) = 1245 nM, K(i)(RARγ) = 53 nM]. In series I, the presence of a phenol group, irrespective of the nature of tertioalkyl group, imparted at least partial RARγ selectivity, whereas in series II, the presence of both adamantyl and phenol groups is needed to confer RARγ selectivity. The RARγ selective ligands induce differentiation in F9 cells (7, AC50 = 33 nM; 19, AC50 = 66 nM). From series I, a mixed RARβ-γ agonist with potent cellular differentiating activity was selected for development as a topical antiacne agent, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (5, CD 271) [K(i)(RARα) = 1100 nM, K(i)-(RARβ) = 34 nM, K(i)(RARγ) = 130 nM, AC50(F9) = 37 nM]. Finally, from series II, we have obtained a weak antagonist in the F9 cellular differentiation assay, 4-[(E)-2-(3-tert-butyl- 4-hydroxyphenyl)propenyl]benzoic acid (15, IC50 = 700 nM).

Benzo (b) thiophene carboxylate derivatives and pharmaceutical compositions

Aromatic heterocyclic derivatives have the formula STR1 wherein R1 represents STR2 wherein R3 represents hydrogen, --OR4 wherein R4 represents hydrogen, alkyl having 1-20 carbon atoms or mono- or polyhydroxyalkyl or R3 represents STR3 wherein r' and r" represent hydrogen, lower alkyl or together form a heterocycle, R2 represents hydrogen or --CH3 and Ar represents STR4 wherein Z is O or S, STR5 wherein R5 is lower alkyl or STR6 wherein R6 is hydrogen or alkyl having 1-10 carbon atoms and R7 represents alkyl having 4-12 carbon atoms or cycloalkyl, Y is CH or a nitrogen atom and X represents oxygen, sulfur or --N--R8 when R8 represents hydrogen, lower alkyl or lower alkoxycarbonyl, with the proviso that (i) when Y is CH and X is oxygen or sulfur Ar is other than C and (ii) when Y is nitrogen and X is oxygen, Ar is other than (C) or (D) in which R6 is alkyl having 1-4 carbon atoms and R7 is branched alkyl having 4-12 atoms useful in veterinary or human therapy and in cosmetic formulations.