116209-31-5

Upstream product

• 99-60-5 2-chloro-4-nitrobenzoic acid 
• 46004-37-9 methyl 4-amino-2-chlorobenzoate 
• 13324-11-3 methyl 2-chloro-4-nitrobenzoate 
• 1190947-66-0 methyl 2-chloro-4-(ethoxycarbonothioylthio)benzoate 
• 2457-76-3 4-amino-2-chlorobenzoic acid 

Downstream Products

• 81542-91-8 2,2'-dichloro-4,4'-dithiobis(benzoic acid) 
• 879088-84-3 methyl 2-chloro-4-mercaptobenzoate 
• 830335-81-4 C₁₈H₁₆Cl₂O₄S₂ 

Relevant academic research and scientific papers

PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE

Piperidine compounds of the Formular: (I) and pharmaceutically acceptable salts thereof, wherein X, Y, R 1, R 2, R 3, L, R 4, L 1, Q and R 5 are as defined herein. The compounds and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

PYRIDYL INHIBITORS OF HEDGEHOG SIGNALLING

The invention provides novel inhibitors of hedgehog signaling that are useful as s therapeutic agent for treating malignancies where the compounds have the general formula (I): where A, X, Y R1, R2, R3, R4, m and n are as described herein.

Pyridyl inhibitors of hedgehog signalling

The invention provides novel inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A, X, Y R1, R2, R3, R4, m and n are as described herein.

Benzoyl ring halogenated classical 2-amino-6-methyl-3,4-dihydro-4-oxo-5- substituted thiobenzoyl-7H-pyrrolo[2,3-d]pyrimidine antifolates as inhibitors of thymidylate synthase and as antitumor agents

In an attempt to circumvent resistance to and toxicity of clinically used folate-based thymidylate synthase (TS) inhibitors that require folylpoly-γ-glutamate synthetase (FPGS) for their antitumor activity, we designed and synthesized two classical 6-5 ring-fused analogues, N-[4-[(2-amino-6-methyl-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)thio] -2′-fluorobenzoyl]-L-glutamic acid (4) and N-[4-[(2-amino-6-methyl-3,4- dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)thio]-2′-chlorobenzoyl] -L-glutamic acid (5), as TS inhibitors and antitumor agents. The key intermediates in the synthesis of these classical analogues were the mercaptans 10 and 11, which were obtained from the corresponding nitro compounds 6 and 7 respectively, by reduction of the nitro groups followed by diazotization of the amines. The syntheses of analogues 4 and 5 were achieved via the oxidative addition of the sodium salt of ethyl 2-halo-substituted-4-mercaptobenzoate (16 or 17) to 2-amino-6-methyl-3,4-dihydro-4-oxo-7H-pyirolo[2,3-d]pyrimidine (18) in the presence of iodine. The esters obtained from the reaction were deprotected and coupled with diethyl-L-glutamate followed by saponification. Compounds 4 and 5 were both more potent inhibitors of human TS (IC50 values of 54 and 51 nM, respectively) than were PDDF and the clinically used ZD1694 and LY231514. Compounds 4 and 5 were not substrates for human FPGS up to 250 μM. In addition, 4 and 5 were growth inhibitory against CCRF-CEM cells as well as a number of other tumor cell lines in culture, and protection studies established TS as the principal target of these analogues.