Category: 865233-35-8

Name: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acidOn October 31, 2012 ,《A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents》 appeared in PLoS One. The author of the article were Luo, Jian; Swaminath, Gayathri; Brown, Sean P.; Zhang, Jane; Guo, Qi; Chen, Michael; Nguyen, Kathy; Tran, Thanhvien; Miao, Lynn; Dransfield, Paul J.; Vimolratana, Marc; Houze, Jonathan B.; Wong, Simon; Toteva, Maria; Shan, Bei; Li, Frank; Zhuang, Run; Lin, Daniel C.-H.. The article conveys some information:

Type 2 diabetes is characterized by impaired glucose homeostasis due to defects in insulin secretion, insulin resistance and the incretin response. GPR40 (FFAR1 or FFA1) is a G-protein-coupled receptor (GPCR), primarily expressed in insulin-producing pancreatic β-cells and incretin-producing enteroendocrine cells of the small intestine. Several GPR40 agonists, including AMG 837 and TAK-875, have been disclosed, but no GPR40 synthetic agonists have been reported that engage both the insulinogenic and incretinogenic axes. In this report we provide a mol. explanation and describe the discovery of a unique and potent class of GPR40 full agonists that engages the enteroinsular axis to promote dramatic improvement in glucose control in rodents. GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes. The improvement in hyperglycemia by AM-1638 was reduced in the presence of the GLP-1 receptor antagonist Ex(9-39)NH2. After reading the article, we found that the author used (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8Name: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid)

(S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8) belongs to alkynes. The addition of nonpolar E−H bonds across C≡C is general for silanes, boranes, and related hydrides. The hydroboration of alkynes gives vinylic boranes which oxidize to the corresponding aldehyde or ketone. In the thiol-yne reaction the substrate is a thiol.Name: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid

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Agarwal, Sameer; Sasane, Santosh; Deshmukh, Prashant; Rami, Bhadresh; Bandyopadhyay, Debdutta; Giri, Poonam; Giri, Suresh; Jain, Mukul; Desai, Ranjit C. published their research in ACS Medicinal Chemistry Letters on December 8 ,2016. The article was titled 《Identification of an Orally Efficacious GPR40/FFAR1 Receptor Agonist》.SDS of cas: 865233-35-8 The article contains the following contents:

GPR40/FFAR1 is a G protein-coupled receptor predominantly expressed in pancreatic β-cells and activated by long-chain free fatty acids, mediating enhancement of glucose-stimulated insulin secretion. A novel series of substituted 3-(4-aryloxyaryl)propanoic acid derivatives were prepared and evaluated for their activities as GPR40 agonists, leading to the identification of compound 5, which is highly potent in in vitro assays and exhibits robust glucose lowering effects during an oral glucose tolerance test in nSTZ Wistar rat model of diabetes (ED50 = 0.8 mg/kg; ED90 = 3.1 mg/kg) with excellent pharmacokinetic profile, and devoid of cytochromes P 450 isoform inhibitory activity. In the experiment, the researchers used (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8SDS of cas: 865233-35-8)

(S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8) belongs to alkynes. The addition of nonpolar E−H bonds across C≡C is general for silanes, boranes, and related hydrides.SDS of cas: 865233-35-8 The hydroboration of alkynes gives vinylic boranes which oxidize to the corresponding aldehyde or ketone. In the thiol-yne reaction the substrate is a thiol.

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Walker, Shawn D.; Borths, Christopher J.; DiVirgilio, Evan; Huang, Liang; Liu, Pingli; Morrison, Henry; Sugi, Kiyoshi; Tanaka, Masahide; Woo, Jacqueline C. S.; Faul, Margaret M. published an article in Organic Process Research & Development. The title of the article was 《Development of a Scalable Synthesis of a GPR40 Receptor Agonist》.Recommanded Product: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid The author mentioned the following in the article:

Early process development and salt selection for AMG 837, a novel GPR40 receptor agonist, is described. The synthetic route to AMG 837 involved the convergent synthesis and coupling of two key fragments, (S)-3-(4-hydroxyphenyl)hex-4-ynoic acid (I) and 3-(bromomethyl)-4′-(trifluoromethyl)biphenyl (II). The chiral β-alkynyl acid I was prepared in 35% overall yield via classical resolution of the corresponding racemic acid (±)-I. An efficient and scalable synthesis of (±)-I was achieved via a telescoped sequence of reactions including the conjugate alkynylation of an in situ protected Meldrum’s acid derived acceptor. The biaryl bromide II was prepared in 86% yield via a 2-step Suzuki-Miyaura coupling-bromination sequence. Chemoselective phenol alkylation mediated by tetrabutylphosphonium hydroxide allowed direct coupling of I and II to afford AMG 837. Due to the poor physiochem. stability of the free acid form of the drug substance, a sodium salt form was selected for early development, and a more stable, crystalline hemicalcium salt dihydrate form was subsequently developed. Overall, the original 12-step synthesis of AMG 837 was replaced by a robust 9-step route affording the target in 25% yield. The experimental part of the paper was very detailed, including the reaction process of (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8Recommanded Product: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid)

(S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8) belongs to alkynes. The addition of nonpolar E−H bonds across C≡C is general for silanes, boranes, and related hydrides.Recommanded Product: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid The hydroboration of alkynes gives vinylic boranes which oxidize to the corresponding aldehyde or ketone. In the thiol-yne reaction the substrate is a thiol.

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《AMG 837: A potent, orally bioavailable GPR40 agonist》 was published in Bioorganic & Medicinal Chemistry Letters in 2012. These research results belong to Houze, Jonathan B.; Zhu, Liusheng; Sun, Ying; Akerman, Michelle; Qiu, Wei; Zhang, Alex J.; Sharma, Rajiv; Schmitt, Michael; Wang, Yingcai; Liu, Jiwen; Liu, Jinqian; Medina, Julio C.; Reagan, Jeff D.; Luo, Jian; Tonn, George; Zhang, Jane; Lu, Jenny Ying-Lin; Chen, Michael; Lopez, Edwin; Nguyen, Kathy; Yang, Li; Tang, Liang; Tian, Hui; Shuttleworth, Steven J.; Lin, Daniel C.-H.. Application In Synthesis of (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid The article mentions the following:

The discovery that certain long chain fatty acids potentiate glucose stimulated insulin secretion through the previously orphan receptor GPR40 sparked interest in GPR40 agonists as potential antidiabetic agents. Optimization of a series of β-substituted phenylpropanoic acids led to the identification of (S)-3-(4-((4′-(trifluoromethyl)biphenyl-3-yl)methoxy)phenyl)hex-4-ynoic acid (AMG 837) as a potent GPR40 agonist with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents. The experimental part of the paper was very detailed, including the reaction process of (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8Application In Synthesis of (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid)

(S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8) belongs to alkynes. The addition of nonpolar E−H bonds across C≡C is general for silanes, boranes, and related hydrides. The hydroboration of alkynes gives vinylic boranes which oxidize to the corresponding aldehyde or ketone. In the thiol-yne reaction the substrate is a thiol.Application In Synthesis of (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts