281235-00-5

Upstream product

• 99-76-3 methyl 4-hydroxylbenzoate 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 
• 118811-07-7 tert-butyl 4-(tosyloxy)piperidin-1-carboxylate 
• 99-75-2 4-methyl-benzoic acid methyl ester 

Downstream Products

• 99764-63-3 Leu-Ser-p-nitro-Phe-Nle-Ala-Leu-OMe*TFA 
• 281234-95-5 methyl 4-(piperidin-4-yloxy)benzoate 
• 1595145-22-4 4-[(1-{6-[(2S)-2-{[2-(4-cyanophenyl)ethyl]carbamoyl}azetidin-1-yl]-2-(trifluoromethyl)pyrimidin-4-yl}piperidin-4-yl)oxy]benzoic acid 
• 321337-38-6 tert-butyl 4-(4-(hydroxymethyl)phenoxy)piperidine-1-carboxylate 
• 952588-99-7 4-(piperidin-4-yloxy)-benzoic acid methyl ester trifluoroacetate 
• 455323-66-7 4'-(methoxycarbonylphenyloxy)-4-piperidine hydrochloride 
• 162046-56-2 4-(1-tert-butoxycarbonylpiperidin-4-yloxy)benzoic acid 
• 455323-68-9 methyl 4-(N-adamantanoyl-4-piperidinyloxy)benzoate 
• 455323-70-3 methyl 4-(N-(diphenyl)carbamoyl-4-piperidinyloxy)benzoate 
• 455323-67-8 methyl 4-(N-(diphenyl)acetyl-4-piperidinyloxy)benzoate 

Relevant academic research and scientific papers

TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS

Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.

Discovery and Development of N-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A Novel, Potent, Selective, and Orally Active Histamine H3 Receptor Inverse Agonist with Robust Wake-Promoting Activity

A series of chemical optimizations guided by in vitro affinity at a histamine H3 receptor (H3R), physicochemical properties, and pharmacokinetics in rats resulted in identification of N-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide dihydrochloride (17v, SUVN-G3031) as a clinical candidate. Compound 17v is a potent (hH3R Ki = 8.73 nM) inverse agonist at H3R with selectivity over other 70 targets, Compound 17v has adequate oral exposures and favorable elimination half-lives both in rats and dogs. It demonstrated high receptor occupancy and marked wake-promoting effects with decreased rapid-eye-movement sleep in orexin-B saporin lesioned rats supporting its potential therapeutic utility in treating human sleep disorders. It had no effect on the locomotor activity at doses several fold higher than its efficacious dose. It is devoid of hERG and phospholipidosis issues. Phase-1 evaluation for safety, tolerability, and pharmacokinetics, and long-term safety studies in animals have been successfully completed without any concern for further development.

HISTONE DEACETYLASE INHIBTORS

Provided herein are compounds and methods for inhibiting histone deacetylase ("HDAC") enzymes (e.g., HDAC1, HDAC2, and HDAC3).

Benzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy

Inhibition of cyclin dependent kinase 2 (CDK2) in complex with cyclin A in G1/S phase of the cell cycle has been shown to promote selective apoptosis of cancer cells through the E2F1 pathway. An alternative approach to catalytic inhibition is to target the substrate recruitment site also known as the cyclin binding groove (CBG) to generate selective non-ATP competitive inhibitors. The REPLACE strategy has been applied to identify fragment alternatives and substituted benzoic acid derivatives were evaluated as a promising scaffold to present appropriate functionality to mimic key peptide determinants. Fragment Ligated Inhibitory Peptides (FLIPs) are described which potently inhibit both CDK2/cyclin A and CDK4/cyclin D1 and have preliminary anti-tumor activity. A structural rationale for binding was obtained through molecular modeling further demonstrating their potential for further development as next generation non ATP competitive CDK inhibitors.

Discovery of trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as potent, orally bioavailable TGR5 (GPBAR1) agonists: Structure-activity relationships, lead optimization, and chronic in vivo efficacy

Activation of the G-protein coupled receptor (GPCR) Takeda G-protein receptor 5 (TGR5), also known as G-protein bile acid receptor 1 (GPBAR1), has been shown to play a key role in pathways associated with diabetes, metabolic syndrome, and autoimmune disease. Nipecotamide 5 was identified as an attractive starting point after a high-throughput screen (HTS) for receptor agonists. A comprehensive hit-to-lead effort culminated in the discovery of 45h as a potent, selective, and bioavailable TGR5 agonist to test in preclinical metabolic disease models. In genetically obese mice (ob/ob), 45h was as effective as a dipeptidyl peptidase-4 (DPP-4) inhibitor at reducing peak glucose levels in an acute oral glucose tolerance test (OGTT), but this effect was lost upon chronic dosing.

Development of novel 2-[4-(aminoalkoxy)phenyl]-4(3H)-quinazolinone derivatives as potent and selective histamine H3 receptor inverse agonists

Novel 2-[4-(aminoalkoxy)phenyl]-4(3H)-quinazolinone derivatives were identified as potent human H3 receptor inverse agonists. After systematic modification of lead 5a, the potent and selective analog 5r was identified. Elimination of hERG K+ channel and human α1A-adrenoceptor activities is the main focus of the present study.

11β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 ACTIVE COMPOUNDS

A novel class of compounds of the general formula (I), their use in therapy, pharmaceutical compositions comprising the compounds, as well as their use in the manufacture of medicaments are described. The present compounds modulate the activity of 11β-hydroxy-steroid dehydrogenase type 1 (11βHSD1) and are accordingly useful in the treatment of diseases in which such a modulation is beneficial, e.g. the metabolic syndrome.

Synthesis and evaluation of 2′-substituted 4-(4′-carboxy- or 4′-carboxymethylbenzylidene)-N-acylpiperidines: Highly potent and in vivo active steroid 5α-reductase type 2 inhibitors

Sixteen compounds derived from N-acyl-4-benzylidenepiperidine-4′-carboxylic acids were synthesized and evaluated for inhibition of rat and human steroid 5α-reductase isozymes types 1 and 2. In the dicyclohexylacetyl series, fluorination in the 2-position of the benzene nucleus (15), exchange of the carboxy group by a carboxymethyl moiety (20), and combination of both structural modifications (25) led to highly active inhibitors of the human type 2 isozyme (IC50 values: 15, 11 nM; 20, 6 nM; 25, 7 nM; finasteride, 5 nM). In vivo all compounds tested markedly reduced the prostate weights in castrated testosterone-treated rats. Oral activity was shown for compound 7. From the finding that compound 15 is active in the rat, although it is a rather poor inhibitor of the rat enzyme and is a strong inhibitor of the human enzyme, it is concluded that it should be highly potent in men.