- Metal-free reduction of unsaturated carbonyls, quinones, and pyridinium salts with tetrahydroxydiboron/water
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A series of unsaturated carbonyls, quinones, and pyridinium salts have been effectively reduced to the corresponding saturated carbonyls, dihydroxybenzenes, and hydropyridines in moderate to high yields with tetrahydroxydiboron/water as a mild, convenient, and metal-free reduction system. Deuterium-labeling experiments have revealed this protocol to be an exclusive transfer hydrogenation process from water. This journal is
- Li, Tiejun,Peng, Henian,Tang, Wenjun,Tian, Duanshuai,Xu, Guangqing,Yang, He
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p. 4327 - 4337
(2021/05/31)
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- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.
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Paragraph 0440; 0443
(2021/04/23)
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- TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS
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Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.
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Page/Page column 308-310
(2020/10/21)
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- CEREBLON BINDERS FOR THE DEGRADATION OF IKAROS
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The present invention provides cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway along with their use in therapeutic applications as described herein.
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Page/Page column 381; 382
(2019/10/23)
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- N-benzyl-tetrahydropyridine compound and preparation method thereof
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The invention provides an N-benzyl-tetrahydropyridine compound and a preparation method thereof, and the preparation method comprises the following steps: S1, adding benzyl bromide into a pyridine compound to carry out nucleophilic substitution reaction t
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Paragraph 0082-0091
(2019/06/30)
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- A comparison between KbH4 and NaBH4 in their reduction of pyridinium salts
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This paper compares potassium borohydride and sodium borohydride in the reduction of pyridinium salts to tetrahydropyridines. The results indicate that potassium borohydride is more suitable for this reaction with low costs, mild reaction conditions and i
- Quan, Hao,Zhu, Bin,Li, Xiaolin,Zhan, Li,Luo, Yu
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p. 1244 - 1250
(2019/12/23)
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- Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of Lead Compound (3 R)-7-Hydroxy- N-[(1 S)-2-methyl-1-(piperidin-1-ylmethyl)propyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (PDTic)
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Past studies have shown that it has been difficult to discover and develop potent and selective κ opioid receptor antagonists, particularly compounds having potential for clinical development. In this study, we present a structure-activity relationship (SAR) study of a recently discovered new class of tetrahydroisoquinoline κ opioid receptor antagonists which led to (3R)-7-hydroxy-N-{(1S)-2-methyl-1-[(-4-methylpiperidine-1-yl)methyl]propyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (12) (4-Me-PDTic). Compound 12 had a Ke = 0.37 nM in a [35S]GTPγS binding assay and was 645- and >8100-fold selective for the κ relative to the μ and δ opioid receptors, respectively. Calculated log BB and CNS (central nervous system) multiparameter optimization (MPO) and low molecular weight values all predict that 12 will penetrate the brain, and pharmacokinetic studies in rats show that 12 does indeed penetrate the brain.
- Ondachi, Pauline W.,Kormos, Chad M.,Runyon, Scott P.,Thomas, James B.,Mascarella, S. Wayne,Decker, Ann M.,Navarro, Hernán A.,Fennell, Timothy R.,Snyder, Rodney W.,Carroll, F. Ivy
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supporting information
p. 7525 - 7545
(2018/09/12)
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- A supporting france for cloth as the starting material of the preparation method (by machine translation)
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The invention discloses a method for supporting france for cloth starting material N - ((3 R, 4 R) - 4 - methyl - 1 - benzyl - 3 - piperidinyl) - N - methyl - 7 - paratoluene sulfonyl - 7 H - pyrrolo [2, 3 - D] pyrimidine - 4 - amine (I) synthetic method, specific steps are as follows: to 4 - methyl pyridine as the starting material, with the benzyl chloride undergo nucleophilic substitution by the 4 - methyl - 1 - phenylmethyl - pyridine hydrochloride, under the action of the sodium borohydride reduction reaction, borohydrite - oxidation reaction, hydroxy oxidation, the introduction of the reductive amination of the stereo selectivity of the two chiral center, through a readily available and inexpensive chiral acid (L - DTTA) splitting, to obtain optically pure intermediates (3 R, 4 R) - (1 - benzyl - 4 - methyl - piperidin - 3 - yl) - methylamine, and finally with the 4 - chloro pyrrolo pyrimidine condensation is obtained. The whole method raw materials are easy, simple operation, after treatment is easy, and the cost is low. (by machine translation)
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- Achieving control over the branched/linear selectivity in palladium-catalyzed allylic amination
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Palladium-catalyzed reaction of unsymmetrical allylic electrophiles with amines gives rise to regioisomeric allylic amines. We have found that linear products result from the thermodynamically controlled isomerization of the initially formed branched products. The isomerization is promoted by protic acid and active palladium catalyst. The use of base shuts down the isomerization pathway and allows for the preparation and isolation of branched allylic amines. Solvent plays a key role in achieving high kinetic regioselectivity and in controlling the rate of isomerization. The isomerization can be combined with ring-closing metathesis to afford the synthesis of exocyclic allylic amines from their endocyclic precursors.
- Dubovyk, Igor,Watson, Iain D. G.,Yudin, Andrei K.
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p. 1559 - 1575
(2013/03/28)
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- Efficient and chemoselective reduction of pyridines to tetrahydropyridines and piperidines via rhodium-catalyzed transfer hydrogenation
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Promoted by iodide anion the rhodium complex dimer, [Cp RhCl 2]2, catalyzes efficiently the transfer hydrogenation of various quaternary pyridinium salts under mild conditions, affording not only piperidines but also 1,2,3,6-tetrahydropyridines in a highly chemoselective fashion, depending on the substitution pattern at the pyridinium ring. The reduction is conducted in azeotropic formic acid/triethylamine (HCOOH-Et 3N) mixture at 40 °C, with catalyst loadings as low as 0.005mol% being feasible. Copyright
- Wu, Jianjun,Tang, Weijun,Pettman, Alan,Xiao, Jianliang
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supporting information
p. 35 - 40
(2013/03/13)
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- Palladium-catalyzed ring-contraction and ring-expansion reactions of cyclic allyl amines
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Ring around the rosy: An amino group can act as the leaving group or the nucleophile in a palladium-catalyzed allylic amination. As a result, readily accessible cyclic amines can be either ring contracted or ring expanded (see scheme).
- Dubovyk, Igor,Pichugin, Dmitry,Yudin, Andrei K.
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p. 5924 - 5926
(2011/08/04)
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- BENZOXAZEPINES AS INHIBITORS OF PI3K/m TOR AND METHODS OF THEIR USE AND MANUFACTURE
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The invention is directed to Compounds of Formula (I): the invention provides compounds that inhibit, regulate, and/or modulate P13K and/or mTOR that are useful in the treatment of hyperproliferative diseases, such as cancer, in mammals. This invention al
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Page/Page column 120-121
(2010/12/26)
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- Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds
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Alkyne compounds having MCH-receptor antagonistic activity, which are useful for preparing pharmaceutical compositions for the treatment of metabolic disorders and/or eating disorders, particularly obesity and diabetes.
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Page/Page column 12
(2008/06/13)
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- NOVEL ALKYNE COMPOUNDS WITH AN MCH-ANTAGONISTIC ACTION AND MEDICAMENTS COMPRISING SAID COMPOUNDS
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The invention relates to individual alkyne compounds with an antagonistic action against the MCH-receptor. Said compounds are suitable for producing medicaments for the treatment of metabolic disorders and/or eating disorders, in particular adiposity and diabetes.
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Page/Page column 38
(2008/06/13)
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- NOVEL ALKYNE COMPOUNDS EXHIBITING AN MCH ANTAGONISTIC EFFECT AND DRUGS CONTAINING SAID COMPOUNDS
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The invention relates to an alkyne compound of general formula (I) in which A, B, W, X, Y, Z, R and R groups and residuals have the meanings given in claim 1. Drugs containing at least one type of inventive alkyne are also disclosed. The inventive drugs exhibiting an MCH-receptor antagonistic activity are suitable for treating metabolic disturbances and/or eating disorders, in particular adiposity, bulimia, anorexia, hyperphagia and diabetes.
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Page/Page column 61-62
(2008/06/13)
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- NOVEL ALKYNE COMPOUNDS WITH AN MCH-ANTAGONISTIC ACTION AND MEDICAMENTS CONTAINING SAID COMPOUNDS
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The invention relates to alkyne compounds of general formula (I), in which the groups and radicals A, B, W, X, Y, Z, R1 and R2 are defined as cited in claim 1. The invention also relates to medicaments containing at least one inventive alkyne. As a result of the antagonistic action against the MCH-receptor, the inventive medicaments are suitable for treating metabolic disorders and/or eating disorders, in particular adiposity and diabetes.
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Page/Page column 63
(2010/02/14)
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- Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds
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The present invention relates to alkyne compounds of general formula I wherein the groups and radicals A, B, W, X, Y, Z, R1 and R2 have the meanings given in claim 1. Moreover the invention relates to pharmaceutical compositions containing at least one alkyne according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity and diabetes.
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Page/Page column 23
(2010/02/14)
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- Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds
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Alkyne compounds of formula I wherein A, B, W, X, Y, Z, R1, and R2 have the meanings given herein, which have MCH-receptor antagonistic activity and are useful for preparing pharmaceutical compositions for the treatment of metabolic disorders and/or eating disorders, particularly obesity and diabetes.
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Page/Page column 23
(2010/02/14)
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- Development of a scaleable route for the production of cis-N-benzyl-3-methylamino-4-methylpiperidine
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The synthesis of cis-N-benzyl-3-methylamino-4-methylpiperidine (5) via hydroboration of tetrahydropyridine 3 followed by oxidation and reductive amination was optimized and scaled up to produce 10-kg quantities of product. Three routes to 3 were identified, and the reduction of pyridinium salt 7 was selected as the most preferable to run on-scale. The hydroboration and oxidative workup were carefully studied to optimize throughput on that transformation, as was the reductive amination.
- Brown Ripin, David H.,Abele, Stefan,Cai, Weiling,Blumenkopf, Todd,Casavant, Jeffrey M.,Doty, Jonathan L.,Flanagan, Mark,Koecher, Christian,Laue, Klaus W.,McCarthy, Keith,Meltz, Cliff,Munchhoff, Mike,Pouwer, Kees,Shah, Bharat,Sun, Jianmin,Teixeira, John,Vries, Ton,Whipple, David A.,Wilcox, Glenn
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p. 115 - 120
(2013/09/05)
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- Pyrrolo[2,3-d]pyrimidine compounds
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A compound of the formula wherein R1, R2 and R3 are as defined above, useful as inhibitors of protein kinases, such as the enzyme Janus Kinase 3.
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- TiCL4 INDUCED IMINIUM ION CYCLIZATIONS OF α-CYANOAMINES
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Tertiary α-cyanoamines served as the precursors of iminium ions in the presence of titanium tetrachloride.Various intramolecular nucleophiles, olefinic and acetylenic, were found to produce cyclized products.The influences of ring sizes and substitutions on the double bonds were also investigated.
- Yang, Teng-Kuei,Hung, Shun-Ming,Lee, Dong-Sheng,Hong, An-Way,Cheng, Chan-Chun
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p. 4973 - 4976
(2007/10/02)
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- 2-Cyano-Δ3-piperideines. 12. Stereochemistry of Formation of N-Benzyl-2-cyano-Δ3-piperideines and Facile Isomerization on Alumina to 2-Cyano-Δ4-piperideines. A Potentially General Route to the Synthesis of 2,6-Disubstitute
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The reaction of the piperideine N-oxides 1a-f with trifluoroacetic anhydride in CH2Cl2 at 0 deg C (Polonovski-Potier reaction) led to the formation of the N-benzyl-2-cyano-Δ3-piperideines 3a-f.Epimeric mixtures were obtained for the amino nitri
- Bonin, Martine,Romero, Jose Ricardo,Grierson, David S.,Husson, Henri-Philippe
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p. 2392 - 2400
(2007/10/02)
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