14676-01-8Relevant articles and documents
Asymmetric synthesis of β-lactam via palladium-catalyzed enantioselective intramolecular c(sp3)-h amidation
Tong, Hua-Rong,Zheng, Wenrui,Lv, Xiaoyan,He, Gang,Liu, Peng,Chen, Gong
, p. 114 - 120 (2020)
β-Lactams are important scaffolds in drug design and frequently used as reactive intermediates in organic synthesis. Catalytic reactions featuring intramolecular C-H amidation of alkyl carboxamide substrates could provide a straightforward disconnection strategy for β-lactam synthesis. Herein, we report a streamlined method for asymmetric synthesis of β-aryl β-lactams from propanoic acid and aryl iodides via Pd-catalyzed sequential C(sp3)-H functionalization. The lactam-forming reaction provides an example of PdII-catalyzed enantioselective intramolecular C(sp3)-H amidation reaction and proceeds up to 94% ee. The use of a 2-methoxy-5-chlorophenyl iodide oxidant is critical to control the competing reductive elimination pathways of the PdIV intermediate to achieve the desired chemoselectivity. Mechanistic studies suggest that both steric and electronic effects of the unconventional aryl iodide oxidant are responsible for controlling the competing C-N versus C-C reductive elimination pathways of the PdIV intermediate.
PRMT5 INHIBITORS AND USES THEREOF
-
Paragraph 00511, (2016/01/12)
Described herein are compounds of Formula (I)-(XIII), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
The insulin secretory action of novel polycyclic guanidines: Discovery through open innovation phenotypic screening, and exploration of structure-activity relationships
Shaghafi, Michael B.,Barrett, David G.,Willard, Francis S.,Overman, Larry E.
supporting information, p. 1031 - 1036 (2014/03/21)
We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3- arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner.
WNT PATHWAY ANTAGONISTS
-
Page/Page column 53-54, (2011/04/26)
The present invention relates to known and novel compounds of formula (I) as herein described and pharmaceutical compositions thereof. The compounds of formula (I) have inhibitory effect on the Wnt pathway and are therefore useful in the preparation of a medicament, in particular for the treatment of cancer.
Basic techniques of working on a solid phase: From ABC of the peptide synthesis to libraries of non-natural amino acids
Babaev,Ermolat'ev
experimental part, p. 2572 - 2589 (2011/04/15)
Libraries of hardly available amino acids bearing a heteroaromatic ring (2-pyrimidyl, substituted 2-pyridyl or 2-thiazolyl) at the amino group were prepared using solid-phase synthesis on various resins. The synthesized compounds are structurally similar to some known antidiabetic drugs. The paper combines features of a review (elementary introduction to the solid-phase synthesis methodology and technique for beginners and selected methods from peptide chemistry) and step-by-step experimental protocols (tested by the authors) useful as a methodic tool. The presented protocols (immobilization and modification of amino acids, placing and removal of common protective groups) require no sophisticated equipment and may be useful as pictorial introductory tasks for students education. Pleiades Publishing, Ltd., 2010.
1,8-Naphthyridine-3-carboxamide derivatives with anticancer and anti-inflammatory activity
Kumar, Vivek,Jaggi, Manu,Singh, Anu T.,Madaan, Alka,Sanna, Vinod,Singh, Pratibha,Sharma, Pramod K.,Irchhaiya, Raghuveer,Burman, Anand C.
experimental part, p. 3356 - 3362 (2009/10/23)
A number of 1-propargyl-1,8-naphthyridine-3-carboxamide derivatives (15-35) have been synthesized and screened for their in vitro cytotoxicity and anti-inflammatory activity. Compounds 22, 31 and 34 have shown high cytotoxicity against a number of cancer cell lines, while compound 24 showed significant anti-inflammatory activity.
GLYT2 MODULATORS
-
Page/Page column 52-53, (2010/02/11)
α-, β-, and γ-amino acid derivatives of formula I are disclosed as selective GlyT2 inhibitors for the treatment of central nervous system (CNS) conditions such as muscle spasticity, tinnitus, epilepsy and neuropathic pain. Formula I
Succinct synthesis of β-amino acids via chiral isoxazolines
Fuller, Amelia A.,Chen, Bin,Minter, Aaron R.,Mapp, Anna K.
, p. 5376 - 5383 (2007/10/03)
β-Amino acids are important synthetic targets due to their presence in a wide variety of natural products, pharmaceutical agents, and mimics of protein structural motifs. While β-amino acids containing geminal substitution patterns have enormous potential for application in these contexts, synthetic challenges to the stereoselective preparation of this class of compound have thus far limited more complete studies. We present here a straightforward method employing chiral isoxazolines as key intermediates to access five different β-amino acid structural types with excellent selectivity. Of particular note is the use of this approach to prepare highly substituted cis-β-proline analogues. The ready access to these diversely substituted compounds is expected to facilitate future studies of the structure and function of this important class of molecules.
Highly diastereoselective and enantioselective preparation of homoallylic amines: Application for the synthesis of β-amino acids and γ-lactams
Ramachandran, P. Veeraraghavan,Burghardt, Thomas E.
, p. 4387 - 4395 (2007/10/03)
Reactions of N-silyl- and N-aluminoimines with B- allyldiisopinocampheylborane in the presence of methanol, followed by oxidative workup furnished homoallylic amines in good yields and high ee. A 11B NMR spectroscopy study revealed that the reactions do not proceed, even at room temperature, unless a molar equivalent of water or methanol is added. The first reagent-controlled asymmetric crotylboration and alkoxyallylboration of aldimines furnishing β-methyl or βalkoxy homoallylic amines in very high diastereoselectivity and enantioselectivity are reported herein. Crotylboration and alkoxyallylboration of imines proceed only with the "allyl"-boron "ate" complexes, instead of the "allyl"-dialkylboron reagents used with aldehydes. The addition of methanol is necessary for these reactions as well. Application of this methodology for the conversion of representative nitriles to β-amino acids in two steps has been described. Additionally, a procedure for the preparation of chiral δ-amino alcohols and γ-lactams from nitriles is also reported.
A concise approach to structurally diverse β-amino acids
Minter, Aaron R.,Fuller, Amelia A.,Mapp, Anna K.
, p. 6846 - 6847 (2007/10/03)
We have demonstrated that the high yields and selectivities of 1,3-dipolar cycloadditions can be translated into facile stereoselective syntheses of a diverse array of β-amino acids, key components of bioactive natural products, β-lactams, and peptidomimetics. Simply by selecting different combinations of three readily available starting materials (an oxime, a chiral allylic alcohol, and a nucleophile), we used the reaction sequence to prepare four different β-amino acid structural types with a variety of substitution patterns in good overall yield. Of particular note is the use of this approach to prepare highly substituted β-amino acids not readily accessible by previously reported methodologies. This will pave the way for future studies of the structure and function of this important class of molecules. Copyright
