195202-02-9

Upstream product

• 178445-80-2 (E)-1-(3,4-dimethoxyphenyl)-3-(3-hydroxyphenyl)prop-2-en-1-one 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 121-71-1 3-Hydroxyacetophenone 
• 102774-86-7 9-fluorenylmethyl N-succinimidyl carbonate 
• 101555-63-9 (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid 
• 178445-86-8 2[[3-(3,4-dimethyoxyphenyl)-1-oxopropyl]phenoxy]acetic acid 1,1-dimethylester 
• 178445-83-5 3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone 
• 3105-95-1 pipecolinic acid 
• 5292-43-3 bromoacetic acid tert-butyl ester 
• 178445-89-1 (R)-1-(3-(tert-butoxycarbonylmethoxy)phenyl)-3-(3,4-dimethoxyphenyl)-propan-1-ol 

Downstream Products

• 1374119-31-9 C₄₀H₄₉NO₁₂ 
• 195513-97-4 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-oxo-2-(3,4,5-tri-methoxyphenyl)acetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 
• 1374119-20-6 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2R)-2-ethyl-1-hydroxy-cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 
• 1374119-21-7 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2S)-2-ethyl-1-hydroxycyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 
• 1374119-22-8 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2S)-1-hydroxy-2-(hydroxylmethyl)cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 
• 1374119-23-9 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2R)-1-hydroxy-2-methyl cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 
• 1374119-24-0 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2S)-1-hydroxy-2-methyl cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 
• 1373829-44-7 2-(3-((R)-1-(((S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carbonyl)oxy)-3-(3,4-dimethoxyphenyl)propyl)phenoxy)acetic acid 
• 1445604-11-4 C₄₃H₄₇NO₁₀ 
• 1445604-02-3 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-oxo-2-(4-phenoxy-phenyl)acetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 
• 1445604-12-5 C₃₇H₄₁Cl₂NO₉ 
• 1445604-03-4 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-oxo-2-(3,5-dichloro-phenyl)acetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid 

Relevant academic research and scientific papers

A bioorthogonal small-molecule-switch system for controlling protein function in live cells

Chemically induced dimerization (CID) has proven to be a powerful tool for modulating protein interactions. However, the traditional dimerizer rapamycin has limitations in certain in vivo applications because of its slow reversibility and its affinity for

Pipecolate-diketoamides for treatment of psychiatric disorders

The present invention relates to compounds having a pipecolate diketoamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable

Pipecolate-sulfonamides for treatment of psychiatric disorders

The present invention relates to compounds having a pipecolate sulfonamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable

PIPECOLATE-DIKETOAMIDES FOR TREATMENT OF PSYCHIATRIC DISORDERS

The present invention relates to compounds having a pipecolate diketoamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate diketoamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

Evaluation of synthetic FK506 analogues as ligands for the FK506-binding proteins 51 and 52

The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified α-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.

Exploration of pipecolate sulfonamides as binders of the FK506-binding proteins 51 and 52

FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products, which tightly bind to most FKBP family members, including FKBP51 and FKBP52. A bioisosteric replacement of the α-ketoamide moiety of rapamycin and FK506 with a sulfonamide was envisaged with the retention of the conserved hydrogen bonds. A focused solid support-based synthesis protocol was developed, which led to ligands with submicromolar affinity for FKBP51 and FKBP52. The molecular binding mode for one sulfonamide analogue was confirmed by X-ray crystallography.

Investigating protein-ligand interactions with a mutant FKBP possessing a designed specificity pocket

Using structure-based design and protein mutagenesis we have remodeled the FKBP12 ligand binding site to include a sizable, hydrophobic specificity pocket. This mutant (F36V-FKBP) is capable of binding, with low or subnanomolar affinities, novel synthetic ligands possessing designed substituents that sterically prevent binding to the wild-type protein. Using binding and structural analysis of bumped compounds, we show here that the pocket is highly promiscuous - capable of binding a range of hydrophobic alkyl and aryl moieties with comparable affinity. Ligand affinity therefore appears largely insensitive to the degree of occupancy or quality of packing of the pocket. NMR spectroscopic analysis indicates that similar ligands can adopt radically different binding modes, thus complicating the interpretation of structure-activity relationships.