205194-12-3

Usage

Uses

Used in Pharmaceutical Industry:
(R)-Ethyl 1-methylpiperidine-3-carboxylate is used as a key intermediate in the synthesis of various pharmaceutical drugs, such as antipsychotics and analgesics. Its unique stereochemistry contributes to the efficacy and selectivity of these medications.
Used as a Chiral Building Block in Organic Chemistry:
In the field of organic chemistry, (R)-Ethyl 1-methylpiperidine-3-carboxylate serves as a chiral building block for the production of enantiomerically pure compounds. This role is vital for creating compounds with specific biological activities and reducing potential side effects associated with non-specific interactions.

InChI:InChI=1/C9H17NO2/c1-3-12-9(11)8-5-4-6-10(2)7-8/h8H,3-7H2,1-2H3/t8-/m1/s1

Upstream product

• 64-18-6 formic acid 
• 25137-01-3 (R)-ethyl nipecotate 
• 50-00-0 formaldehyd 

Downstream Products

• 952480-19-2 (R)-1-methylpiperidine-3-carboxylic acid 
• 205194-11-2 (R)-3-hydroxymethyl-1-methylpiperidine 

Relevant academic research and scientific papers

Design and evaluation of novel piperidine HIV-1 protease inhibitors with potency against DRV-resistant variants

A novel class of HIV-1 protease inhibitors with flexible piperidine as the P2 ligand was designed with the aim of improving extensive interactions with the active subsites. Many inhibitors exhibited good to excellent inhibitory effect on enzymatic activity and viral infectivity. In particular, inhibitor 3a with (R)-piperidine-3-carboxamide as the P2 ligand and 4-methoxybenzenesulfonamide as the P2’ ligand showed an enzyme Ki value of 29 pM and antiviral IC50 value of 0.13 nM, more than six-fold enhancement of activity compared to DRV. Furthermore, there was no significant change in potency against DRV-resistant mutations and HIV-1NL4?3 variant for 3a. Besides, inhibitor 3a exhibited potent antiviral activity against subtype C variants with low nanomole EC50 values. In addition, the molecular modeling revealed important hydrogen bonds and other favorable van der Waals interactions with the backbone atoms of the protease and provided insight for designing and optimizing more potent HIV-1 protease inhibitors.

Piperidine scaffold as the novel P2-ligands in cyclopropyl-containing HIV-1 protease inhibitors: Structure-based design, synthesis, biological evaluation and docking study

A series of potent HIV-1 protease inhibitors, containing diverse piperidine analogues as the P2-ligands, 4-substituted phenylsulfonamides as the P2'-ligands and a hydrophobic cyclopropyl group as the P1'-ligand, were designed, synthesized and evaluated in this work. Among these twenty-four target compounds, many of them exhibited excellent activity against HIV-1 protease with half maximal inhibitory concentration (IC50) values below 20 nM. Particularly, compound 22a containing a (R)-piperidine-3-carboxamide as the P2-ligand and a 4-methoxylphenylsulfonamide as the P2'-ligand exhibited the most effective inhibitory activity with an IC50 value of 3.61 nM. More importantly, 22a exhibited activity with inhibition of 42% and 26% against wild-type and Darunavir (DRV)-resistant HIV-1 variants, respectively. Additionally, the molecular docking of 22a with HIV-1 protease provided insight into the ligand-binding properties, which was of great value for further study.

QUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS

The invention relates to the use of compounds of the formula I: wherein ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which optionally may contain 1-3 heteroatoms selected independently from O, N and S; Z is -O-, -NH-, -S-, -CH2- or a direct bond; n is 0-5; m is 0-3; R represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NRR (wherein R and R, which may be the same or different, each represents hydrogen or C1-3alkyl), or RX- (wherein X and R are as defined herein; R represents hydrogen, oxo, halogeno, hydroxy, C1-4alkoxy, C1-4alkyl, C1-4alkoxymethyl, C1-4alkanoyl, C1-4haloalkyl, cyano, amino, C2-5alkenyl, C2-5alkynyl, C1-3alkanoyloxy, nitro, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, N-(C1-4alkylsulphonyl)amino, N-(C1-4alkylsulphonyl)-N-(C1-4alkyl)amino, N,N-di(C1-4alkylsulphonyl)amino, a C3-7alkylene chain joined to two ring C carbon atoms, C1-4alkanoylaminoC1-4alkyl, carboxy or a group RX (wherein X and R are as defined herein); and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

Novel 4-anilinoquinazolines with C-7 basic side chains: Design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors

We have previously shown that 4-anilinoquinazolines can be potent inhibitors of vascular endothelial growth factor (VEGF) receptor (Flt-1 and KDR) tyrosine kinase activity. A novel subseries of 4-anilinoquinazolines that possess basic side chains at the C-7 position of the quinazoline nucleus have been synthesized. This subseries contains potent, nanomolar inhibitors of KDR (median IC50 0.02 μM, range 0.001-0.04 μM), which are comparatively less potent vs Flt-1 tyrosine kinase (median IC50 0.55 μM, range 0.02-1.6 μM). The compounds also retain some inhibitory activity against the tyrosine kinase associated to the endothelial growth factor receptor (EGFR) (median IC50 0.2 μM, range 0.075-0.8 μM) but demonstrate selectivity vs that associated to the FGF receptor 1 (median IC50 2.5 μM, range 0.9-19 μM). This selectivity profile is also evident in a growth factor-stimulated human endothelial cell (HUVEC) proliferation assay (i.e., inhibition of VEGF > EGF > FGF), with inhibition of VEGF-induced proliferation being achieved at nanomolar concentrations (median IC50 0.06 μM). Further examination of compound 2 (ZD6474) in recombinant enzyme assays revealed excellent selectivity for the inhibition of KDR tyrosine kinase (IC50 0.04 μM) vs the kinase activity of erbB2, MEK, CDK-2, Tie-2, IGFR-1R, PDK, PDGFRβ, and AKT (IC50 range: 1.1 to > 100 μM). Anilinoquinazolines possessing basic C-7 side chains exhibited markedly improved aqueous solubility over previously described anilinoquinazolines possessing neutral C-7 side chains (up to 500-fold improvement at pH 7.4). In addition, aqueous solubility of the neutral fraction present at pH 7.4 of the basic subseries of anilinoquinazoline proved to be higher than that of the neutral analogue 1 (ZD4190). Oral administration of representative compounds to mice (50 mg/kg) produced plasma levels between 0.2 and 3 μM at 24 h after dosing. Our development candidate 2 demonstrated a very attractive in vitro profile combined with excellent solubility (330 μM at pH 7.4) and good oral bioavailability in rat and dog (> 80 and > 50%, respectively). This compound demonstrated highly significant, dose-dependent, antitumor activity in athymic mice. Once daily oral administration of 100 mg/kg of compound 2 for 21 days inhibited the growth of established Calu-6 lung carcinoma xenografts by 79% (P 0.001, Mann Whitney rank sum test), and substantial inhibition (36%, P 0.02) was evident with 12.5 mg/kg/day.