130418-90-5

Usage

Uses

Used in Pharmaceutical Industry:
1-Pyrrolidinecarboxylic acid, 2-ethynyl-, 1,1-dimethylethyl ester, (2R)is used as a therapeutic agent for the treatment of epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. Its application is based on its ability to modulate the release of neurotransmitters such as glutamate, norepinephrine, and substance P, thereby reducing neuronal excitability and pain signal transmission.

InChI:InChI=1/C11H17NO2/c1-5-9-7-6-8-12(9)10(13)14-11(2,3)4/h1,9H,6-8H2,2-4H3/t9-/m0/s1

Upstream product

• 109-72-8 n-butyllithium 
• 130419-38-4 (S)-2-(2,2-dibromoethenyl)-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester 
• 90965-06-3 dimethyl 1-(1-diazo-2-oxopropyl)phosphonate 
• 115186-37-3 tert-butyl (2S)-2-{[N-methoxy(N-methyl)amino]carbonyl}pyrrolidine-1-carboxylate 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 558-13-4 carbon tetrabromide 
• 69610-41-9 Boc-L-Pro-H 
• 27491-70-9 dimethyl diazomethylphosphonate 
• 21047-57-4 diethyl (1-diazo-2-oxopropyl)phosphonate 
• 4202-14-6 dimethyl (2-oxopropyl)phosphonate 
• 147-85-3 L-proline 
• 23356-96-9 (S)-1-Pyrrolidin-2-yl-methanol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 

Downstream Products

• 922529-40-6 ethyl 4-[2-[1-(tert-butoxycarbonyl)-(2S)-pyrrolidinyl]ethynyl]phenylacetate 
• 881691-88-9 tert-butyl (S)-1-(4-(benzyloxy)benzyl)-2-((S)-2-ethynylpyrrolidin-1-yl)-2-oxoethylcarbamate 
• 833473-69-1 (S)-tert-butyl-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidine-1-carboxylate 
• 1201915-86-7 (S)-2-(1-phenyl-1H-1,2,3-triazol-4-yl)pyrrolidine-1-carboxylic acid tert-butyl ester 
• 1445590-37-3 (S)-tert-butyl 2-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)pyrrolidine-1-carboxylate 
• 833473-71-5 C₃₀H₂₈ClFN₄O₃S 
• 130523-68-1 *,S^*)>-2-<3-(1-pyrrolidinyl)-1-propynyl>-1-(3,3,3-trifluoro-2-methoxy-1-oxo-2-phenylpropyl)pyrrolidine 
• 130523-70-5 *,S^*)>-2-<3-(dimethylamino)-1-propynyl>-1-(3,3,3-trifluoro-2-methoxy-1-oxo-2-phenylpropyl)pyrrolidine 
• 1242094-60-5 C₁₇H₂₁BrN₂O₂ 

Relevant academic research and scientific papers

The design of 8-hydroxyquinoline tetracyclic lactams as HIV-1 integrase strand transfer inhibitors

A novel series of HIV-1 integrase strand transfer inhibitors were designed using the venerable two-metal binding pharmacophore model and incorporating structural elements from two different literature scaffolds. This manuscript describes a number of 8-hyd

POTENT HUMAN NEURONAL NITRIC OXIDE SYNTHASE INHIBITORS

Disclosed are 2-aminopyridine derivative compounds for use as inhibitors of nitric oxide synthase (NOS). In particular, the field of the invention relates to 2-aminopyridine derivative compounds for use as inhibitors of neuronal nitric oxide synthase (nNOS), which are formulated as pharmaceutical compositions for treating diseases and disorders associated with nNOS such as Alzheimer's, Parkinson's, and Huntington's diseases, and amytrophic lateral sclerosis, cerebral palsy, stroke/ischemic brain damage, and migraine headaches.

From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs

The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone (6), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (fu brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone (42), a DORA with improved in vivo efficacy compared to 6.

Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having a 2-Aminopyridine Scaffold

Effective delivery of therapeutic drugs into the human brain is one of the most challenging tasks in central nervous system drug development because of the blood-brain barrier (BBB). To overcome the BBB, both passive permeability and efflux transporter liability of a compound must be addressed. Herein, we report our optimization related to BBB penetration of neuronal nitric oxide synthase (nNOS) inhibitors toward the development of new drugs for neurodegenerative diseases. Various approaches, including enhancing lipophilicity and rigidity of new inhibitors and modulating the pKa of amino groups, have been employed. In addition to determining inhibitor potency and selectivity, crystal structures of most newly designed compounds complexed to various nitric oxide synthase isoforms have been determined. We have discovered a new analogue (21), which exhibits not only excellent potency (Ki 30 nM) in nNOS inhibition but also a significantly low P-glycoprotein and breast-cancer-resistant protein substrate liability as indicated by an efflux ratio of 0.8 in the Caco-2 bidirectional assay.

Synthesis and thermo-responsive behavior of helical polyacetylenes derived from proline

A series of optically active helical poly[(S)-2-ethynyl-N-aliphatic acylpyrrolidine] were efficiently synthesized from a commercially available biomass-based starting material, and that bearing a short propionyl substituent exhibited an unexpected lower critical solution temperature in an aqueous solution with a narrow phase-transition window and a small hysteresis.

Series of Alkynyl-Substituted Thienopyrimidines as Inhibitors of Protozoan Parasite Proliferation

Discovery of new chemotherapeutic lead agents can be accelerated by optimizing chemotypes proven to be effective in other diseases to act against parasites. One such medicinal chemistry campaign has focused on optimizing the anilinoquinazoline drug lapatinib (1) and the alkynyl thieno[3,2-d]pyrimidine hit GW837016X (NEU-391, 3) into leads for antitrypanosome drugs. We now report the structure-activity relationship studies of 3 and its analogs against Trypanosoma brucei, which causes human African trypanosomiasis (HAT). The series was also tested against Trypanosoma cruzi, Leishmania major, and Plasmodium falciparum. In each case, potent antiparasitic hits with acceptable toxicity margins over mammalian HepG2 and NIH3T3 cell lines were identified. In a mouse model of HAT, 3 extended life of treated mice by 50%, compared to untreated controls. At the cellular level, 3 inhibited mitosis and cytokinesis in T. brucei. Thus, the alkynylthieno[3,2-d]pyrimidine chemotype is an advanced hit worthy of further optimization as a potential chemotherapeutic agent for HAT.

PYRROLOBENZODIAZEPINE ANTIBODY DRUG CONJUGATES AND METHODS OF USE

The invention provides antibody-drug conjugates comprising an antibody conjugated to a pyrrolobenzodiazepine drug moiety via a disulfide linker, pyrrolobenzodiazepine linker-drug intermediates, and methods of using the antibody-drug conjugates.

As cell necrosis inhibitors of the indole compounds (by machine translation)

The invention relates to chemical formula (1) indole compounds, or its pharmaceutically acceptable salt or isomer, and in containing the same as the characteristic, as an active ingredient for the prevention or treatment of cell necrosis and its associated disease composition and method of manufacturing. (by machine translation)

INDOLE COMPOUND AS INHIBITOR OF NECROSIS

The present invention relates to an indole compound represented by formula (1), a pharmaceutically acceptable salt or isomer thereof, a composition for prevention or treatment of necrosis and necrosis-associated diseases, and a method for preparing the composition, the composition comprising the indole compound or the pharmaceutically acceptable salt or isomer thereof as an active ingredient.

1,2,3-Triazole Stabilized Neurotensin-Based Radiopeptidomimetics for Improved Tumor Targeting

Neurotensin (NT) is a regulatory peptide with nanomolar affinity toward NT receptors, which are overexpressed by different clinically relevant tumors. Its binding sequence, NT(8-13), represents a promising vector for the development of peptidic radiotracers for tumor imaging and therapy. The main drawback of the peptide is its short biological half-life due to rapid proteolysis in vivo. Herein, we present an innovative strategy for the stabilization of peptides using nonhydrolizable 1,4-disubstituted, 1,2,3-triazoles as amide bond surrogates. A triazole scan?of the peptide sequence yielded novel NT(8-13) analogues with enhanced stability, retained receptor affinity, and improved tumor targeting properties in vivo. The synthesis of libraries of triazole-based peptidomimetics was achieved efficiently on solid support by a combination of Fmoc-peptide chemistry, diazo transfer reactions, and the Cu(I)-catalyzed alkyne azide cycloaddition (CuAAC) employing methods that are fully compatible with standard solid phase peptide synthesis (SPPS) chemistry. Thus, the amide-to-triazole substitution strategy may represent a general methodology for the metabolic stabilization of biologically active peptides.