72057-18-2

Upstream product

• 17012-21-4 1-benzylpyrrolidine-3-carboxylic acid methyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 272443-90-0 methyl 6-ethoxy-5,6-dihydro-4H-1,2-oxazine-4-carboxylate 
• 50-00-0 formaldehyd 
• 292638-85-8 acrylic acid methyl ester 
• 56-40-6 glycine 
• 51535-00-3 methyl 1-benzyl-5-oxo-3-pyrrolidinecarboxylate 
• 67-56-1 methanol 
• 59378-87-9 pyrrolidine-3-carboxylic acid 
• 122684-33-7 methyl 1-tert-butoxycarbonyl-3-pyrrolidinecarboxylate 
• 216311-58-9 methyl (S)-(+)-1-(phenylmethyl)-3-pyrrolidinecarboxylate 
• 216311-59-0 methyl (R)-(-)-1-(phenylmethyl)-3-pyrrolidinecarboxylate 
• 428518-36-9 methyl (R)-(-)-1-(phenylmethyl)-5-oxo-3-pyrrolidinecarboxylate 
• 428518-44-9 methyl (S)-1-(phenylmethyl)-5-oxo-3-pyrrolidinecarboxylate 

Downstream Products

• 1446492-16-5 C₂₇H₃₀ClFN₂O₆ 
• 1446492-18-7 C₂₇H₃₀ClFN₂O₆ 
• 179020-59-8 methyl 1-[2-[4-(phenylmethyl)phenoxy]ethyl]-3-pyrrolidinecarboxylate 
• 72925-16-7 1-boc-pyrrolidine-3-carboxylic acid 

Relevant academic research and scientific papers

X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson’s Disease

Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) have been closely linked to the pathogenesis of Parkinson’s disease (PD); nevertheless, development of dual hIDO1 and hTDO inhibitors to evaluate their potential efficacy against PD is still lacking. Here, we report biochemical, biophysical, and computational analyses revealing that 1H-indazole-4-amines inhibit both hIDO1 and hTDO by a mechanism involving direct coordination with the heme ferrous and ferric states. Crystal structure-guided optimization led to23, which manifested IC50values of 0.64 and 0.04 μM to hIDO1 and hTDO, respectively, and had good pharmacokinetic properties and brain penetration in mice.23showed efficacy against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse motor coordination deficits, comparable to Madopar, an anti-PD medicine. Further studies revealed that different from Madopar,23likely has specific anti-PD mechanisms involving lowering IDO1 expression, alleviating dopaminergic neurodegeneration, reducing inflammatory cytokines and quinolinic acid in mouse brain, and increasing kynurenic acid in mouse blood.

Fused ring compound, pharmaceutical composition containing fused ring compound, and preparation method and application of fused ring compound

The present invention relates to a fused ring compound as shown in Formula (I-A) or Formula (I-B) which is described in the specification, a pharmaceutical composition comprising the same, a preparation method and an application in the prevention or treatment of diseases or conditions associated with RET activity.

Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox

Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.

THERAPEUTIC INHIBITORY COMPOUNDS

The invention provides compounds of Formula I and Formula II: A-B-C-D-E-F-G-J (I) C-D-E-F-G-J (II) wherein A, B, C, D, E, F, G, and J have any of the values defined in the specification, and salts thereof. The compounds are useful for inhibiting plasma kallikrein, and for treating a disease or condition in an animal where inhibition of plasma kallikrein is indicated.

Novel phosphorus radical-based routes to horsfiline

(Chemical Equation Presented) Radicals derived from the phosphorus reagents, ethylpiperidine hypophosphite (EPHP) and diethylphosphine oxide (DEPO), are used in two related approaches to synthesis of the alkaloid horsfiline (1). In particular, DEPO proves

Design and synthesis of conformationally constrained 3-(N-alkylamino) propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) receptors

A series of conformationally constrained analogs of 3 were synthesized and evaluated as S1P receptor agonists. Several novel scaffolds were identified as suitable for further investigation. A series of conformationally constrained 3-(N-alkylamino)propylphosphonic acids were systematically synthesized and their activities as S1P receptor agonists were evaluated. Several pyrrolidine and cyclohexane analogs had S1P receptor profiles comparable to the acyclic lead compound, 3-(N-tetradecylamino)propylphosphonic acid (3), lowered circulating lymphocytes in mice after iv administration and were thus identified as being suitable for further investigations.

4-substituted quinoline derivatives, method and intermediates for their preparation and pharmaceutical compositions containing them

The invention relates to 4-substituted quinoline compounds of general formula: which are active as antimicrobials, in which: X1, X2, X3, X4 and X5 is C—R′1, to C—R′5 respectively

LTA4 Hydrolase inhibitors

The present invention provides compounds of the formula Ar1-Q-Ar2-Y-R-Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB4 production, such as proriasis, ulcerative colitis, IBD and asthma.

Preparation of cyclic and bicyclic β-amino acids derivatives from methyl 6-ethoxy-5,6-dihydro-4h-1,2-oxazine-4-carboxylate

The readily available methyl 6-ethoxy-5,6-dihydro-4H-1,2-oxazine-4-carboxylate (1) was alkylated at C-4 and acylated at the nitrogen atom. 1,2-Oxazine 1 and the resulting new substituted 1,2-oxazines 2 and 3 were suitable precursors for the preparation of derivatives of β-proline, nipecotic acid, as well as indolizine-6- and quinolizine-3-carboxylic acids.