137281-08-4

Usage

Uses

Used in Pharmaceutical Applications:
Propanamide, N-(4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylis used as a potential drug candidate for the development of pharmaceuticals targeting specific biological pathways or interactions. Its unique structure and properties may contribute to the creation of novel therapeutic agents.
Used in Research and Development:
In the field of chemical research, Propanamide, N-(4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylis used as a subject of study to explore its chemical properties, potential interactions with biological systems, and possible applications in drug discovery. Propanamide, N-(4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylmay serve as a valuable tool for researchers in the pharmaceutical industry, aiding in the advancement of new drug candidates and therapeutic strategies.

InChI:InChI=1/C11H14N4O2/c1-11(2,3)9(17)15-10-13-7-6(4-5-12-7)8(16)14-10/h4-5H,1-3H3,(H3,12,13,14,15,16,17)

Upstream product

• 3282-30-2 pivaloyl chloride 
• 7355-55-7 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 
• 1538-75-6 2,2-dimethylpropanoic anhydride 
• 63026-85-7 2,6-diamino-5-(3,3-diethoxyethyl)pyrimidin-4(3H)-one 
• 173850-03-8 2-(pivaloylamino)-4(3H)-oxo-7-acetyl-7H-pyrrolo<2,3-d>pyrimidine 

Downstream Products

• 848698-31-7 C₂₁H₂₀ClN₅O 
• 1394818-93-9 C₁₈H₁₈ClIN₄O 
• 502160-41-0 diethyl N-{4-[2-(2-pivaloylamino-4-ethylpyrrolo[2,3-d]pyrimidin-5-yl)ethynyl]benzoyl}-L-glutamate 
• 502160-46-5 diethyl N-{4-[2-(2-pivaloylamino-4-ethylpyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamate 
• 149765-17-3 diethyl N-<2-pivaloylamino-4-chloro<(pyrrolo<2,3-d>pyrimidin-5-yl)ethynyl>benzoyl>-L-glutamate 
• 149765-16-2 N-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethyl-propionamide 
• 149765-15-1 N-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethyl-propionamide 
• 173850-04-9 2-(pivaloylamino)-4(3H)-oxo-7-tosyl-7H-pyrrolo<2,3-d>pyrimidine 
• 151937-08-5 dimethyl N-<4-<2-(2-pivaloylamino-4(3H)-oxo-7H-pyrrolo<2,3-d>pyrimidin-6-yl)ethyl>benzoyl>-L-glutamate 
• 151937-07-4 dimethyl N-<4-<2-(2-pivaloylamino-4(3H)-oxo-7H-pyrrolo<2,3-d>)pyrimidine-6-yl>ethynyl>-L-glutamate 
• 173850-16-3 (S)-2-{4-[2-(2,2-Dimethyl-propionylamino)-7-ethoxycarbonyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-ylethynyl]-benzoylamino}-pentanedioic acid dimethyl ester 

Relevant academic research and scientific papers

Discovery of amide-bridged pyrrolo[2,3-d]pyrimidines as tumor targeted classical antifolates with selective uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis

We previously showed that classical 6-substituted pyrrolo[2,3-d]pyrimidine antifolates bind to folate receptor (FR) α and the target purine biosynthetic enzyme glycinamide ribonucleotide formyltransferase (GARFTase) with different cis and trans conformations. In this study, we designed novel analogs of this series with an amide moiety in the bridge region that can adopt both the cis and trans lowest energy conformations. This provides entropic benefit, by restricting the number of side-chain conformations of the unbound ligand to those most likely to promote binding to FRα and the target enzyme required for antitumor activity. NMR of the most active compound 7 showed both cis and trans amide bridge conformations in ~1:1 ratio. The bridge amide group in the best docked poses of 7 in the crystal structures of FRα and GARFTase adopted both cis and trans conformations, with the lowest energy conformations predicted by Maestro and evidenced by NMR within 1 kcal/mol. Compound 7 showed ~3-fold increased inhibition of FRα-expressing cells over its non-restricted parent analog 1 and was selectively internalized by FRα over the reduced folate carrier (RFC), resulting in significant in vitro antitumor activity toward FRα-expressing KB human tumor cells. Antitumor activity of 7 was abolished by treating cells with adenosine but was incompletely protected by 5-aminoimidazole-4-carboxamide (AICA) at higher drug concentrations, suggesting GARFTase and AICA ribonucleotide formyltransferase (AICARFTase) in de novo purine biosynthesis as the likely intracellular targets. GARFTase inhibition by compound 7 was confirmed by an in situ cell-based activity assay. Our results identify a “first-in-class” classical antifolate with a novel amide linkage between the scaffold and the side chain aryl L-glutamate that affords exclusive selectivity for transport via FRα over RFC and antitumor activity resulting from inhibition of GARFTase and likely AICARFTase. Compound 7 offers significant advantages over clinically used inhibitors of this class that are transported by the ubiquitous RFC, resulting in dose-limiting toxicities.

A Dideazatetrahydrofolate Analogue Lacking a Chiral Center at C-6, N-pyrimidin-5-yl)ethyl>benzoyl>-L-glutamic Acid, Is an Inhibitor of Thymidylate Synthase

N-pyrimidin-5-yl)ethyl>benzoyl>-L-glutamic acid (15), prepared in five steps from 2-pivaloyl-7-deazaguanine, has been found to be an antitumor agent with its primary site of action at thymidylate synthase

MONOCYCLIC, THIENO, PYRIDO, AND PYRROLO PYRIMIDINE COMPOUNDS AND METHODS OF USE AND MANUFACTURE OF THE SAME

The present invention provides monocyclic, thieno, pyrido and pyrrolo pyrimidine compounds. Pharmaceutical compositions comprising one or more of these compounds and optionally comprising a pharmaceutically acceptable salt or hydrate of one or more of the compounds are provided. Preferably, these pharmaceutical compositions further comprise at least one pharmaceutically acceptable carrier. Methods of treating a patient having cancer are provided wherein a therapeutically effective amount of one or more of these compounds or pharmaceutical compositions are administered to the patient.

EC144 is a potent inhibitor of the heat shock protein 90

Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl) methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90α binding assay (IC50 = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC 50 = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qd× 5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.

ALKYNYL PYRROLOPYRIMIDINES AND RELATED ANALOGS AS HSP90-INHIBITORS

Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders. Methods of synthesis and use of such compounds are also described and claimed.

Specific inhibitors in vitamin biosynthesis. Part 10. Synthesis of 7- and 8-substituted 7-deazaguanines

Versatile syntheses of 7- and 8-substituted 7-deazaguanines including N-alkyl derivatives have been developed by identifying selective annulation reactions with 2,6-diaminopyrimidin-4(3H)-one as substrate and β-halocarbonyl compounds as electrophiles. A new synthesis of 8-substituted 7-deazaguanines using nitrosoalkenes as electrophiles is described. With some combinations of reactants, furo[2,3-d]pyrimidines are significant products in place of or in addition to the required 7-deazaguanines [pyrrolo[2,3-d]-pyrimidin-4(3H)-ones]. When 2,4-diamino-6-chloropyrimidine was used as a substrate, imidazo-pyrimidines were produced.

Synthesis of N-{4-[2-(2-amino-5,6-dihydro-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-6-y l)-ethyl]benzoyl}-L-glutamic acid: A ring-contracted analogue of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid

This paper describes the synthesis of N-{4-[2-(2-amino-5,6-dihydro-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-6-y l)ethyl]benzoyl}-L-glutamic acid (4), which can be viewed as a ring-contracted analogue of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF, 1) in which the C-7 methylene group of the latter has been excised and C-6 joined to N-8. This compound exhibits significant activity as an inhibitor of the growth of human (CCRF-CEM) lymphoblastic leukemic cells in vitro and apparently acts by blocking de novo purine biosynthesis through inhibition of glycinamide ribonucleotide formyltransferase (GAR FTase).