287193-00-4

Usage

Application

tert-butyl 3-ethynylpyrrolidine-1-carboxylate is a useful research chemical.

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

Upstream product

• 27491-70-9 dimethyl diazomethylphosphonate 
• 59379-02-1 tert-butyl 3-formylpyrrolidine-1-carboxylate 
• 90965-06-3 dimethyl 1-(1-diazo-2-oxopropyl)phosphonate 
• 21047-57-4 diethyl (1-diazo-2-oxopropyl)phosphonate 

Relevant academic research and scientific papers

Discovery of a Candidate Containing an (S)-3,3-Difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1 H-inden Scaffold as a Highly Potent Pan-Inhibitor of the BCR-ABL Kinase including the T315I-Resistant Mutant for the Treatment of Chronic Myeloid Leukemia

BCR-ABL kinase inhibition is an effective strategy for the treatment of chronic myeloid leukemia (CML). Herein, we report compound 3a-P1, bearing a difluoro-indene scaffold, as a novel potent pan-inhibitor against BCR-ABL mutants, including the most refractory T315I mutant. As the privileged (S)-isomer compared to its (R)-isomer 3a-P2, 3a-P1 exhibited potent antiproliferative activities against K562 and Ku812 CML cells and BCR-ABL and BCR-ABLT315I BaF3 cells, with IC50 values of 0.4, 0.1, 2.1, and 4.7 nM, respectively. 3a-P1 displayed a good safety profile in a battery of assays, including single-dose toxicity, hERG K+, and genotoxicity. It also showed favorable mice pharmacokinetic properties with a good oral bioavailability (32%), a reasonable half-life (4.61 h), and a high exposure (1386 h·ng/mL). Importantly, 3a-P1 demonstrated a higher potency than ponatinib in a mice xenograft model of BaF3 harboring BCR-ABLT315I. Overall, the results indicate that 3a-P1 is a promising drug candidate for the treatment of CML to overcome the imatinib-resistant T315I BCR-ABL mutation.

Compound with degrading STAT3 enzyme and preparation method and pharmaceutical application thereof

The present invention relates to a compound represented by general formula (I) or a stereoisomer thereof. Use of deuterated, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or co-crystals, and intermediates and preparation methods, and in STAT3-related diseases such as tumors. B-L-K(I).

QUINAZOLINE DERIVATIVES AS TYROSINE KINASE INHIBITOR, COMPOSITIONS, METHODS OF MAKING THEM AND THEIR USE

The present disclosure relates to new compounds or pharmaceutically acceptable salts or stereoisomers thereof of formula I as inhibitors of receptor tyrosine kinases (RTK), in particular extracellular mutants of ErbB-receptors. The present disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the treatment of cancer in mammals (e.g. humans).

1-CYANO-PYRROLIDINE DERIVATIVES AS DUB INHIBITORS

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R1a, R1b, R1c, R1d, R1e and R1f each independently represent hydrogen, optionally substituted C1-C6 alkyl or optionally substituted C3-C4 cycloalkyl, or R1b and R1c together form an optionally substituted C3-C6 cycloalkyl ring, or R1d and R1e together form an optionally substituted C3-C6 cycloalkyl ring; R2 represents hydrogen or optionally substituted C1-C6 alkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.

Discovery of (S)-3-(3-(3,5-Dimethyl-1 H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis

A series of 3-aryl(pyrrolidin-1-yl)butanoic acids were synthesized using a diastereoselective route, via a rhodium catalyzed asymmetric 1,4-addition of arylboronic acids in the presence of (R)-BINAP to a crotonate ester to provide the (S) absolute configuration for the major product. A variety of aryl substituents including morpholine, pyrazole, triazole, imidazole, and cyclic ether were screened in cell adhesion assays for affinity against αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8 integrins. Numerous analogs with high affinity and selectivity for the αvβ6 integrin were identified. The analog (S)-3-(3-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid hydrochloride salt was found to have very high affinity for αvβ6 integrin in a radioligand binding assay (pKi = 11), a long dissociation half-life (7 h), very high solubility in saline at pH 7 (>71 mg/mL), and pharmacokinetic properties commensurate with inhaled dosing by nebulization. It was selected for further clinical investigation as a potential therapeutic agent for the treatment of idiopathic pulmonary fibrosis.

IMIDAZOPYRAZINES AS LSD1 INHIBITORS

The present invention is directed to imidazo[1,2-a]pyrazine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

TRIAZOLOPYRIDINES AND TRIAZOLOPYRAZINES AS LSD1 INHIBITORS

The present invention is directed to [1,2,4]triazolo[1,5-a]pyridine and [1,2,4]triazolo[1,5-a]pyrazine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

PYRROLO[2,3-B]PYRIDINE CDK9 KINASE INHIBITORS

Disclosed are compounds of Formula (IIa), wherein R1, R2, R3A, R3B, R3C, R3D, R3E, and R4 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions comprising one or more compounds of Formula (IIa)

6,7,8,9-TETRAHYDRO-5H-1,4,7,10A-TETRAAZA-CYCLOHEPT[F]INDENE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS, THEIR USE AND PROCESSES FOR PREPARING THEM

The present invention relates to compounds defined by formula (I), wherein the groups X, Y, W and R 1 to R 4 are defined as in claim 1, possessing valuable pharmacological activity. Particularly the compounds are agonists of the 5-HT2C receptor, and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this receptor, such as metabolic and CNS-related disorders

Substituted bicyclic derivatives useful as anticancer agents

The invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts and solvates thereof, wherein A, X, R1, R3and R4are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals with administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.