Day: February 22, 2023

Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable 纬-Secretase Modulator was written by Peng, Hairuo;Talreja, Tina;Xin, Zhili;Cuervo, J. Hernan;Kumaravel, Gnanasambandam;Humora, Michael J.;Xu, Lin;Rohde, Ellen;Gan, Lawrence;Jung, Mi-young;Shackett, Melanie N.;Chollate, Sowmya;Dunah, Anthone W.;Snodgrass-Belt, Pamela A.;Arnold, H. Moore;Taveras, Arthur G.;Rhodes, Kenneth J.;Scannevin, Robert H.. And the article was included in ACS Medicinal Chemistry Letters in 2011.Application of 4045-30-1 This article mentions the following:

We have investigated a novel series of acid-derived 纬-secretase modulators as a potential treatment of Alzheimer’s disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent 纬-secretase modulator, which lowered A尾42, increased A尾38, but had little to no effect on A尾40 levels both in vitro and in vivo. In addition, compound 10a did not affect Notch signaling in our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic parameters in multiple species. Oral administration of 10a significantly reduced brain A尾42 levels in CF-1 mice and Fischer rats, as well as plasma A尾42 levels in cynomolgus monkeys. Compound 10a was selected as a candidate for preclin. safety evaluation. In the experiment, the researchers used many compounds, for example, 4,4-Dimethylpiperidine (cas: 4045-30-1Application of 4045-30-1).

4,4-Dimethylpiperidine (cas: 4045-30-1) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Application of 4045-30-1

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Thin-layer chromatography of lactones, lactams, and thiolactones was written by Korte, Friedhelm;Vogel, Juergen. And the article was included in Journal of Chromatography in 1962.Quality Control of 1-Acetylpiperidin-2-one This article mentions the following:

These compounds are separated on thin layers of silica gel G with iso-Pr₂O, 80:20 iso-Pr₂O:EtOAc or 20:80 or 60:40 iso-Pr₂O:isooctane as solvent systems. Lactones were detected by conversion to their hydroxamates, which were sprayed with HOAc and 10% aqueous FeCl₃ to give brown spots. Lactams were detected with Dragendorff reagent; thiolactones were split with NaOH, and the resulting SH groups colored with Na nitroprusside. R_f values are tabulated for numerous compounds of these classes with 3 solvent systems. In the experiment, the researchers used many compounds, for example, 1-Acetylpiperidin-2-one (cas: 3326-13-4Quality Control of 1-Acetylpiperidin-2-one).

1-Acetylpiperidin-2-one (cas: 3326-13-4) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Quality Control of 1-Acetylpiperidin-2-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Development of a new bicyclic imidazole nucleophilic organocatalyst for direct enantioselective C-acylation was written by Zhou, Muxing;He, Ende;Zhang, Lu;Chen, Jianzhong;Zhang, Zhenfeng;Liu, Yangang;Zhang, Wanbin. And the article was included in Organic Chemistry Frontiers in 2019.Application In Synthesis of 1,2,2,6,6-Pentamethylpiperidine This article mentions the following:

A novel chiral nucleophilic organocatalyst I easily synthesized from simple starting materials bearing a 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine skeleton has been developed and successfully applied in the direct enantioselective C-acylation of 3-substituted benzofuranones II (R¹ = Me, Et, Pr; R² = H; R³ = H, Me, Et, i-Pr, t-Bu, MeO, Ph; R⁴ = H, Me, Et, i-Pr, t-Bu, MeO, Ph; R⁵ = H, Me, Et, t-Bu, i-Pr; R²R³ = CH=CH-CH=CH; R⁴R⁵ = CH=CH-CH=CH). Its catalytic efficiency was shown to be comparable to that of the previously reported chiral 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole catalyst. A wide range of 3,3-disubstituted benzofuranones (S)-III possessing a quaternary stereocenter, were synthesized with high yields and enantioselectivities. In the experiment, the researchers used many compounds, for example, 1,2,2,6,6-Pentamethylpiperidine (cas: 79-55-0Application In Synthesis of 1,2,2,6,6-Pentamethylpiperidine).

1,2,2,6,6-Pentamethylpiperidine (cas: 79-55-0) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Application In Synthesis of 1,2,2,6,6-Pentamethylpiperidine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening was written by Wellaway, Christopher R.;Amans, Dominique;Bamborough, Paul;Barnett, Heather;Bit, Rino A.;Brown, Jack A.;Carlson, Neil R.;Chung, Chun-wa;Cooper, Anthony W. J.;Craggs, Peter D.;Davis, Robert P.;Dean, Tony W.;Evans, John P.;Gordon, Laurie;Harada, Isobel L.;Hirst, David J.;Humphreys, Philip G.;Jones, Katherine L.;Lewis, Antonia J.;Lindon, Matthew J.;Lugo, Dave;Mahmood, Mahnoor;McCleary, Scott;Medeiros, Patricia;Mitchell, Darren J.;O’Sullivan, Michael;Le Gall, Armelle;Patel, Vipulkumar K.;Patten, Chris;Poole, Darren L.;Shah, Rishi R.;Smith, Jane E.;Stafford, Kayleigh A. J.;Thomas, Pamela J.;Vimal, Mythily;Wall, Ian D.;Watson, Robert J.;Wellaway, Natalie;Yao, Gang;Prinjha, Rab K.. And the article was included in Journal of Medicinal Chemistry in 2020.Related Products of 144222-22-0 This article mentions the following:

The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET-KAc binding has emerged as an attractive therapeutic strategy with a number of small mol. inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochem., pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technol., with an N-Me pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Related Products of 144222-22-0).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Related Products of 144222-22-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

N-cyclic quaternary ammonium-functionalized anion exchange membrane with improved alkaline stability enabled by aryl-ether free polymer backbones for alkaline fuel cells was written by Wang, Xin;Sheng, Weibing;Shen, Yinghua;Liu, Lei;Dai, Sheng;Li, Nanwen. And the article was included in Journal of Membrane Science in 2019.Name: 4-Ethynylpiperidine hydrochloride This article mentions the following:

To realize highly stable anion exchange membrane for alk. fuel cells, aryl-ether free polystyrene (PS) was employed as polymer backbone and functionalized with alk. stable N-cyclic quaternary ammonium (QA), e.g. six-membered (DMP) and bis-six-membered N-cyclic QA (ASU) cations via “click chem.”. Surprisingly, aryl-ether free PS backbone having ASU cation displayed excellent chem. resistance in 1 M NaOH CD₃OD/D₂O solution at 80掳C even for 3000 h without obvious degradation, as confirmed by NMR spectroscopy. After blending with poly(styrene-ethylene-co-butylene-styrene) (SEBS) copolymer which improved the film-forming ability due to the poor mech. properties of PS, the ASU-based blended membrane (SEBS/PS-ASU) having SEBS polymer of 10 wt% possessed the hydroxide conductivity of 31.6 mS/cm with an ion exchange capacity (IEC) of 1.76 meq./g. This value was higher than the blended membrane having DMP cations (25.8 mS/cm with a IEC of 1.92 meq./g). Similar behavior has been observed for the PPO system having the same functional cations. It was believed that the high water uptake of ASU-based membrane resulted in the higher ion conductivity Remarkably, 92.4% of initial hydroxide conductivity was retained for SEBS/PS-ASU membrane with aryl-ether free PS backbone after storage in 1 M NaOH at 80掳C for 900 h, indicating the higher alk. stability over the AEM counterpart with aromatic PPO polymer backbones having aryl ether bonds (21.0% retention in conductivity under the same test conditions). And the accelerated stability test in 5 M NaOH at 80掳C demonstrated that only 16.8% of loss in conductivity was observed after 1800 h of testing for the blend AEMs having ASU cations. Furthermore, as ionomers in catalyst layers, the ASU-functionalized PS copolymers showed a peak power d. of 130 mW/cm² at a c.d. of 210 mA/cm². In the experiment, the researchers used many compounds, for example, 4-Ethynylpiperidine hydrochloride (cas: 550378-30-8Name: 4-Ethynylpiperidine hydrochloride).

4-Ethynylpiperidine hydrochloride (cas: 550378-30-8) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Name: 4-Ethynylpiperidine hydrochloride

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Design and synthesis of Grp94 selective inhibitors based on Phe199 induced fit mechanism and their anti-inflammatory effects was written by Xu, Shicheng;Guo, Anping;Chen, Nan-nan;Dai, Wei;Yang, Huan-aoyu;Xie, Wenqin;Wang, Mengjie;You, Qi-Dong;Xu, Xiao-Li. And the article was included in European Journal of Medicinal Chemistry in 2021.Category: piperidines This article mentions the following:

Glucose-regulated protein 94 (Grp94), a member of the Heat shock protein 90 (Hsp90) family, is implicated in many human diseases, including cancer, neurodegeneration, inflammatory, and infectious diseases. Here, we describe our effort to design and develop a new series of Grp94 inhibitors based on Phe199 induced fit mechanism. Using an alkynyl-containing inhibitor as a starting point, we developed compound 4 (I), which showed potent inhibitory activity toward Grp94 in a fluorescence polarization-based assay. With improved physicochem. properties and suitable pharmacokinetic properties, compound 4 was advanced into in vivo bioactivity evaluation. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 4 showed anti-inflammatory property and reduced the levels of pro-inflammatory cytokines (TNF-伪 and IL-6). Together, these findings provide evidence that this approach may be promising for further Grp94 drug development efforts. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Category: piperidines).

1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT₄ receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer’s disease was written by Nirogi, Ramakrishna;Mohammed, Abdul Rasheed;Shinde, Anil K.;Bogaraju, Narsimha;Gagginapalli, Shankar Reddy;Ravella, Srinivasa Rao;Kota, Laxman;Bhyrapuneni, Gopinadh;Muddana, Nageswara Rao;Benade, Vijay;Palacharla, Raghava Chowdary;Jayarajan, Pradeep;Subramanian, Ramkumar;Goyal, Vinod Kumar. And the article was included in European Journal of Medicinal Chemistry in 2015.Recommanded Product: Ethyl N-Boc-4-methylpiperidine-4-carboxylate This article mentions the following:

Alzheimer’s disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine₄ receptor (5-HT₄R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo[1,5-a] pyridine derivatives as 5-HT₄R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound I as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition. In the experiment, the researchers used many compounds, for example, Ethyl N-Boc-4-methylpiperidine-4-carboxylate (cas: 189442-87-3Recommanded Product: Ethyl N-Boc-4-methylpiperidine-4-carboxylate).

Ethyl N-Boc-4-methylpiperidine-4-carboxylate (cas: 189442-87-3) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Recommanded Product: Ethyl N-Boc-4-methylpiperidine-4-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Investigational immunosuppressants in early-stage clinical trials for the treatment of multiple sclerosis was written by Gajofatto, Alberto;Turatti, Marco. And the article was included in Expert Opinion on Investigational Drugs in 2018.Safety of 1-(4-(((6-Amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)piperidin-1-yl)prop-2-en-1-one This article mentions the following:

: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale.: The aim of the present article is to review ongoing or recently completed clin. trials investigating immunosuppressive drugs for MS. The websites clinicaltrials.gov, clinicaltrialsregister.eu, and pubmed.gov were searched for phase 1, phase 2, and phase 3 trials starting from 2012. Twelve drugs were identified, including seven monoclonal antibodies and five small mols.: Current or recently completed trials of immunosuppressants for MS are mainly proof-of-concept studies enrolling patients with relapsing disease and using efficacy endpoints based on magnetic resonance imaging measures of inflammatory activity. Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies represent the most commonly investigated drugs, suggesting that mechanisms of action that have already shown promise for MS treatment are being exploited to find new therapies with improved safety, tolerability, and convenience of dosing. Clin. trials of immunosuppressants for progressive MS are largely lacking. In the experiment, the researchers used many compounds, for example, 1-(4-(((6-Amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)piperidin-1-yl)prop-2-en-1-one (cas: 1415823-73-2Safety of 1-(4-(((6-Amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)piperidin-1-yl)prop-2-en-1-one).

1-(4-(((6-Amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)piperidin-1-yl)prop-2-en-1-one (cas: 1415823-73-2) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Safety of 1-(4-(((6-Amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)piperidin-1-yl)prop-2-en-1-one

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Exploring the 3-piperidin-4-yl-1H-indole scaffold as a novel antimalarial chemotype was written by Santos, Sofia A.;Lukens, Amanda K.;Coelho, Lis;Nogueira, Fatima;Wirth, Dyann F.;Mazitschek, Ralph;Moreira, Rui;Paulo, Alexandra. And the article was included in European Journal of Medicinal Chemistry in 2015.Application of 17403-09-7 This article mentions the following:

A series of 3-piperidin-4-yl-1H-indoles with building block diversity was synthesized based on a hit derived from an HTS whole-cell screen against Plasmodium falciparum. Thirty-eight compounds were obtained following a three-step synthetic approach and evaluated for antiparasitic activity. The SAR shows that 3-piperidin-4-yl-1H-indole is intolerant to most N-piperidinyl modifications. Nevertheless, the authors were able to identify a new compound with lead-like properties (MW = 305; cLogP = 2.42), showing antimalarial activity against drug-resistant and sensitive strains (EC₅₀ values 鈭?3 渭M), selectivity for malaria parasite and no cross-resistance with chloroquine, thus representing a potential new chemotype for further optimization towards novel and affordable antimalarial drugs. The synthesis of the target compounds was achieved using 3-(4-piperidinyl)-1H-indole and 4,6-dichloroquinoline as key reactants. In the experiment, the researchers used many compounds, for example, 3-(Piperidin-4-yl)-1H-indole (cas: 17403-09-7Application of 17403-09-7).

3-(Piperidin-4-yl)-1H-indole (cas: 17403-09-7) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Application of 17403-09-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Solanum alkaloids. L. Optical rotatory dispersion and circular dichroism. 1. Dithiourethans of cyclic amines was written by Ripperger, H.;Schreiber, K.. And the article was included in Tetrahedron in 1965.Synthetic Route of C6H13N This article mentions the following:

The dithiourethans of substituted piperidines with an asym. C atom were prepared and their optical rotatory dispersion as well as their circular dichroism were measured. The uv, O.R.D. and circular dichroism spectra were measured at 20掳 in dioxane. The amine (1 mole), 8 moles Et₃N and CS₂ in alc. kept 30 min. at 50掳 and 1 hr. at 50掳 after addition of 16 moles MeI and the mixture evaporated at 50掳 in vacuo gave the corresponding dithiourethans. The compounds were very unstable and could not be purified chromatographically on Al₂O₃. Resolution with L-tartaric acid gave 0.99 g. (R)-伪-pipecoline, m. 118-21掳, [伪]¹⁹_D -31.8掳, converted in 20 ml. alc. and extracted with Et₂O to yield 44% (R)-N-dithiocarbomethoxy-伪-pipecoline, b_1.0 150-60掳. Conhydrine (143 mg.), m. 119-20掳, [伪]²⁰_D 9.9掳 (95% alc.) treated as above using 2 ml. EtOH and the product decomposed with H₂O and extracted with Et₂O yielded 14% N-dithiocarbomethoxyconhydrine, m. 25掳. Conversion of 104 mg. (22S, 25R)-22,26-imino-5伪-cholestane-3尾,16尾-diol using 30 ml. alc. yielded 46% N-dithiocarbomethoxydihydro-5伪-solasodan-3尾-ol A, m. 203-5掳. Dioxane (10 ml.) containing 104 mg. (22S, 25S)-22,26-imino-5伪-cholestane-3尾,16尾-diol kept 15 hrs. at 20掳 with 10 mg. NaOH in 0.25 ml. H₂O and 21 mg. CS₂, the mixture treated 15 hrs. at 20掳 with 145 mg. MeI and evaporated at 50掳 in vacuo yielded 54% N-dithiocarbomethoxydihydro-5伪-tomatidan-3尾-ol A, m. 133-6掳, (R)-Pipecolinic acid (1 millimole), m. 264掳, [伪]²⁰_D 28掳 (H₂O) in 3 ml. H₂O shaken 1 hr. at 20掳 with 2 ml. N NaOH and 114 mg. CS₂ and the mixture shaken 2 hrs. with 218 mg. MeI, the Et₂O-washed solution decomposed with 1 ml. N HCl and extracted with Et₂O yielded 52% (R)-N-dithiocarbomethoxypipecolinic acid, m. 88.0-90.5掳. Dihydro-5伪-tomatidan-3尾-ol B (104 mg.) converted in the presence of 10 ml. alc. yielded 35% N-dithiocarbomethoxydihydro-5伪-tomatidan-3尾-ol B, m. 143-5掳. The molar amplitude, a, of the O.R.D. curves and the maximum molar ellipsity, [胃]_maximum, of the dithiourethans were tabulated. The range of compounds investigated suggested that only the asym. at the 伪-C atom was important in determining the sign of the Cotton effect, and this correlation appeared to be generally useful in the assignment of the absolute 伪-configuration of cyclic amines. In the experiment, the researchers used many compounds, for example, (R)-2-Methylpiperidine (cas: 1722-95-8Synthetic Route of C6H13N).

(R)-2-Methylpiperidine (cas: 1722-95-8) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Synthetic Route of C6H13N

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem