- Sustainable Route Toward N-Boc Amines: AuCl3/CuI-Catalyzed N-tert-butyloxycarbonylation of Amines at Room Temperature
-
N-tert-butoxycarbonyl (N-Boc) amines are useful intermediates in synthetic/medicinal chemistry. Traditionally, they are prepared via an indirect phosgene route with poor atom economy. Herein, a step- and atom-economic synthesis of N-Boc amines from amines, t-butanol, and CO was reported at room temperature. Notably, this N-tert-butyloxycarbonylation procedure utilized ready-made substrates, commercially available AuCl3/CuI as catalysts, and O2 from air as the sole oxidant. This catalytic system provided unique selectivity for N-Boc amines in good yields. More significantly, gram-scale preparation of medicinally important N-Boc amine intermediates was successfully implement, which demonstrated a potential application prospect in industrial syntheses. Furthermore, this approach also showed good compatibility with tertiary and other useful alcohols. Investigations of the mechanisms revealed that gold catalyzed the reaction and copper acted as electron transfer mediator in the catalytic cycle.
- Cao, Yanwei,He, Lin,Huang, Yang
-
-
- Iodoarene-Catalyzed Oxyamination of Unactivated Alkenes to Synthesize 5-Imino-2-Tetrahydrofuranyl Methanamine Derivatives
-
Reported here is the room-temperature metal-free iodoarene-catalyzed oxyamination of unactivated alkenes. In this process, the alkenes are difunctionalized by the oxygen atom of the amide group and the nitrogen in an exogenous HNTs2 molecule. This mild and open-air reaction provided an efficient synthesis to N-bistosyl-substituted 5-imino-2-tetrahydrofuranyl methanamine derivatives, which are important motifs in drug development and biological studies. Mechanistic study based on experiments and density functional theory calculations showed that this transformation proceeds via activation of the substrate alkene by an in situ generated cationic iodonium(III) intermediate, which is subsequently attacked by an oxygen atom (instead of nitrogen) of amides to form a five-membered ring intermediate. Finally, this intermediate undergoes an SN2 reaction by NTs2 as the nucleophile to give the oxygen and nitrogen difunctionalized 5-imino-2-tetrahydrofuranyl methanamine product. An asymmetric variant of the present alkene oxyamination using chiral iodoarenes as catalysts also gave promising results for some of the substrates.
- Deng, Xiao-Jun,Liu, Hui-Xia,Zhang, Lu-Wen,Zhang, Guan-Yu,Yu, Zhi-Xiang,He, Wei
-
p. 235 - 253
(2021/01/09)
-
- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
-
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.
- -
-
Paragraph 0382-0384
(2021/04/23)
-
- Design and Synthesis of 56 Shape-Diverse 3D Fragments
-
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol?1 above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3D fragments with six commercial libraries, it is clear that our collection has high three-dimensionality and shape diversity.
- Atobe, Masakazu,Blakemore, David C.,Bond, Paul S.,Chan, Ngai S.,De Fusco, Claudia,Downes, Thomas D.,Firth, James D.,Hubbard, Roderick E.,Jones, S. Paul,Klein, Hanna F.,O'Brien, Peter,Roughley, Stephen D.,Vidler, Lewis R.,Waddelove, Laura,Whatton, Maria Ann,Wheldon, Mary C.,Woolford, Alison J.-A.,Wrigley, Gail L.
-
-
- Preparation method of 2-(4-piperidyl)-2-propanol and hydrochloride thereof
-
The invention provides a preparation method of 2-(4-piperidyl)-2-propanol and hydrochloride thereof. The method comprises the following steps: introducing tert-butyloxycarboryl as an amino protectiongroup on a raw material 4-piperidinecarboxylate molecule, carrying out alkylation addition on an ester group in the raw material molecule by using a methyl Grignard reagent, removing a BOC protectiongroup in an acidolysis manner to obtain 2-(4-piperidinyl)-2-propanol hydrochloride, and adding an alkali to adjust the pH value in order to obtain 2-(4-piperidinyl)-2-2-propanol. The preparation method provided by the invention is simple, easy to operate and high in yield, has the cost advantage and is very suitable for industrial production.
- -
-
Paragraph 0032-0034
(2020/09/12)
-
- C10-ALKYLENE SUBSTITUTED 13-MEMBERED MACROLIDES AND USES THEREOF
-
Provided are 13-membered macrolides for the treatment of infectious diseases. The 13-membered macrolides described herein are azaketolides. Also provided are methods for preparing the 13- membered macrolides, pharmaceutical compositions comprising the 13-membered macrolides, and methods of treating infectious diseases, and in particular, disease resulting from Gram negative bacteria using the disclosed macrolides. Formula (I)
- -
-
Paragraph 00315
(2020/06/10)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders as well as other disorders.
- -
-
Page/Page column 25; 26
(2019/08/26)
-
- Copper-Catalyzed and Indium-Mediated Methoxycarbonylation of Unactivated Alkyl Iodides with Balloon CO
-
This work emphasizes the synthesis of alkyl esters via Cu-catalyzed and In-mediated alkoxycarbonylation of unactivated alkyl iodides in the presence of In or InI. The reactions were suitable for the preparation of primary, secondary, and even tertiary alkyl esters, representing an exceptionally rare example for the creation of quaternary carbon centers upon formation of esters. The preliminary mechanistic studies indicated that alkyl radicals were involved, and Cu/In/CO played a cooperative role in the carbonylation event.
- Chen, Yanchi,Su, Lei,Gong, Hegui
-
supporting information
p. 4689 - 4693
(2019/06/27)
-
- Light-Mediated Formal Radical Deoxyfluorination of Tertiary Alcohols through Selective Single-Electron Oxidation with TEDA2+.
-
The synthesis of tertiary alkyl fluorides through a formal radical deoxyfluorination process is described herein. This light-mediated, catalyst-free methodology is fast and broadly applicable allowing for the preparation of C?F bonds from (hetero)benzylic, propargylic, and non-activated tertiary alcohol derivatives. Preliminary mechanistic studies support that the key step of the reaction is the single-electron oxidation of cesium oxalates—which are readily available from the corresponding tertiary alcohols—with in situ generated TEDA2+. (TEDA: N-(chloromethyl)triethylenediamine), a radical cation derived from Selectfluor.
- Aguilar Troyano, Francisco José,Ballaschk, Frederic,Jaschinski, Marcel,?zkaya, Yasemin,Gómez-Suárez, Adrián
-
supporting information
p. 14054 - 14058
(2019/11/11)
-
- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
-
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
- -
-
-
- INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL
-
Compounds of Formula I and the pharmaceutically acceptable salts thereof are provided as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
- -
-
-
- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
-
The present invention provides compounds of Formula I (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
- -
-
-
- Quinoline multi-target kinase inhibitor with antitumor activity and preparation method thereof
-
The invention relates to a quinoline multi-target kinase inhibitor with antitumor activity and a preparation method thereof. A general structural formula of the compound is shown in a formula (I) described in the specification. In vitro cell experiments verify that the compound provided by the invention has strong in vitro inhibitory activity on five common tumor cell lines, namely human thyroid carcinoma SW579, human hepatic carcinoma HepG2, human lung adenocarcinoma A549, human colorectal adenocarcinoma HCT116 and human gastric carcinoma MKN45, antitumor activities of most of target compounds are better than or equivalent to that of a positive control drug Cabozantinib, and the in vitro cell experiments verify that the compound provided by the invention has strong inhibitory activity on two kinases KDR and MET, so that the compound provided by the invention has a broad application prospect in preparation of a new antitumor drug.
- -
-
Paragraph 0120; 0121
(2016/10/08)
-
- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
-
The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir11) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
- -
-
-
- COMPOUNDS AND METHODS
-
The present invention relates to novel retinoid-related orphan receptor gamma (RORy) modulators and their use in the treatment of diseases mediated by RORy.
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-
Page/Page column 57
(2013/03/26)
-
- S1P MODULATING AGENTS
-
Compounds of formula (I) or (II) can modulate the activity of SIP receptors.
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-
Page/Page column 121
(2012/08/28)
-
- Synthesis of novel substituted 3,8,11-triazaspiro[5,6]dodecan-7-ones
-
A synthesis of novel substituted 3,8,11-triazaspiro[5,6]dodecan-7-ones using a combination of solution-phase and solid-phase chemistries is described. A solution-phase approach was used to produce a key piperidine intermediate that was then incorporated into a solid-phase synthesis. The combined synthetic strategy was applied to provide a series of substituted 3,8,11-triazaspiro[5,6] dodecan-7-ones in good yield and high purity.
- Qin, Lan-Ying,Cole, Andrew G.,Metzger, Axel,Saionz, Kurt W.,Henderson, Ian
-
scheme or table
p. 849 - 852
(2011/03/20)
-
- Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents
-
A library of 3,5-disubstituted-1,2,4-oxadiazoles 7-9 and their bioisosters, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16, were synthesized and evaluated in vitro for their anticancer potential against a panel of six human cancer cell lines. The key step in the synthesis of oxadiazoles 7-9 involve coupling of amidoxime 6 with an appropriate carboxylic acid followed by thermal cyclization. The bioisosteres, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16 were prepared from the reaction of a common precursor diacylhydrazine 13 with thionyl chloride and Lawesson′s reagent, respectively. The anticancer studies on the synthesized compounds revealed that presence of a cyclopentyloxy or n-butyloxy on the C-3 aryl ring and piperdin-4-yl or trichloromethyl at the C-5 position of 1,2,4-oxadiazole is essential for good activity. In particular, 1,2,4-oxadiazole 7i and analogue 1,3,4-thiadiazole 16 exhibited significant activity against DU145 (IC50: 9.3 μM) and MDA-MB-231 (IC 50: 9.2 μM) cell lines, respectively.
- Kumar, Dalip,Patel, Gautam,Chavers, Angela K.,Chang, Kuei-Hua,Shah, Kavita
-
scheme or table
p. 3085 - 3092
(2011/07/08)
-
- PYRAZINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS
-
Pyrazine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
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-
Page/Page column 179-180
(2010/06/15)
-
- Substituted Spiroamine Compounds
-
Substituted spiroamine compounds corresponding to the formula (I) In which m, n, o, p, Q, r, s, t, R1, R2, R3, R4a, R4b, R5a, R5b, R6a, R6b, R7, R8, R9, R10 and R11 have defined meanings; a process for the preparation of such compounds, pharmaceutical compositions containing such compounds and the use of substituted spiroamines for the treatment or inhibition of pain and/or other conditions mediated by the bradykinin 1 receptor.
- -
-
Page/Page column 36
(2010/05/13)
-
- Efficient synthesis and identification of novel propane-1,3-diamino bridged CCR5 antagonists with variation on the basic center carrier
-
By employing pharmacophore-based design and the privileged fragments reassembly, a series of piperidine-/tropane-/piperazine-bridged CCR5 antagonists were designed and synthesized via an efficient convergent synthesis strategy, with focus on the optimal choice of the basic center carrier structure. Significantly, the 4-amino-4-methylpiperidine bridged 1-acyl-1,3-propanediamine compounds were identified as a new class of nanomolar CCR5 antagonists, providing an efficient approach and novel scaffolds for further development of potent CCR5 inhibitors.
- Fan, Xing,Zhang, Hu-Shan,Chen, Li,Long, Ya-Qiu
-
scheme or table
p. 2827 - 2840
(2010/08/22)
-
- ANTAGONISTS OF PGD2 RECEPTORS
-
Described herein are compounds and pharmaceutical compositions containing such compounds that antagonize the PGD2 activated chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2). Also described herein are methods of using such CRTH2 antagonists, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2 mediated conditions or diseases.
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-
Page/Page column 70-71
(2009/06/27)
-
- NEW PYRIDINE ANALOGUES
-
The present invention relates to certain new pyridin analogues of Formula (I) Chemical formula should be inserted here. Please see paper copy Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
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Page/Page column 107
(2008/06/13)
-
- SUBSTITUTED CYCLOHEXYL DERIVATIVES AS NK-3 RECEPTOR ANTAGONISTS
-
The present invention relates to the compounds of formula (I): wherein A,B, n, X, Y, Z, R1, R2, R3, R4, R5, R6, R7 and R8 are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them and their use in treating diseases mediated by neurokinin-3 (NK-3) receptors. These compounds can thus be used in methods of treatment to suppress and treat such disorders.
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Page/Page column 27
(2010/11/25)
-
- A distal methyl substituent attenuates mitochondrial protein synthesis inhibition in oxazolidinone antibacterials
-
Oxazolidinone analogs bearing substituted piperidine or azetidine C-rings are described. Analogs with a methyl group at the 3-position of the azetidine ring or the 4-position of the piperidine ring exhibited reduced mitochondrial protein synthesis inhibition while retaining good antibacterial potency.
- Renslo, Adam R.,Atuegbu, Andy,Herradura, Prudencio,Jaishankar, Priyadarshini,Ji, Mingzhe,Leach, Karen L.,Huband, Michael D.,Dermyer, Michael R.,Wu, Luping,Vara Prasad,Gordeev, Mikhail F.
-
p. 5036 - 5040
(2008/03/13)
-
- HETEROCYCLIC AMIDE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
-
Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type or T-type calcium channel activity are disclosed. Specifically, a series of heterocyclic amides are disclosed of the general formula (I) where Z is N or CHNR2 and X is NR2, O, S, S=O or SO2. Among other definitions for R, R1, W and Y, the compounds of formula (1) are further characterized by at least one of W or Y being CR3Ar2 where Ar is an aromatic or heteroaromatic ring (for example, where W or Y is a benzhydryl moiety).
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-
Page/Page column 36-37
(2008/06/13)
-
- ALKYLQUINOLINE AND ALKYLQUINAZOLINE KINASE MODULATORS
-
The invention is directed to alkylquinoline and alkylquinazoline compounds of Formula I: wherein R1, R2, R3, B, Z, G, Q and X are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and/or c-kit and/or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and/or c-kit and/or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 and/or c-kit and/or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.
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Page/Page column 51
(2010/11/25)
-
- INHIBITORS OF TRYPTASE
-
The present invention related to certain inhibitors of tryptase that are inhibitors of tryptase, pharmaceutical composition comprising these compounds and method of treating asthma, allergic rhinitis, and/or Chronic Obstructive Pulmonary Disease utilizing these compounds.
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Page/Page column 160
(2008/06/13)
-
- Urea derivatives as calcium channel blockers
-
Urea derivatives which comprise piperidine or piperazine rings and further substitution are effective in ameliorating conditions characterized by unwanted calcium ion channel activity.
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Page/Page column 18
(2010/10/20)
-
- Pyridine, pyrimidine, quinoline, quinazoline, and naphthalene urotensin-II receptor antagonists
-
The present invention relates to urotensin II receptor antagonists, pharmaceutical compositions containing them and their use.
- -
-
-
- Cyclopentyl modulators of chemokine receptor activity
-
Cyclopentyl compounds of Formula (I) are modulators of chemokine receptor activity: wherein D, G, R2, R3 and R8 in Formula (I) are defined herein. The compounds, and pharmaceutically acceptable salts and individual diastereomers thereof, are useful in the treatment and prevention of HIV infection, in delaying the onset of AIDS, and in the treatment of AIDS. The compounds are also useful for treating other diseases and conditions mediated by chemokine receptors.
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Page/Page column 51; 57-58
(2008/06/13)
-
- Synthesis of functionalized nitrogen heterocycles by radical decarboxylation of β- and γ-amino acids
-
Iodinated or oxygenated nitrogen heterocycles are obtained by radical decarboxylation of β- and γ-amino acids. This mild, versatile reaction is applied to the synthesis of bioactive products, such as 4-arylpiperidines, hydroxylated piperidines, and new antifungal agents.
- Boto, Alicia,Hernandez, Rosendo,De Leon, Yolanda,Murguia, Jose R.,Rodriguez-Afonso, Abigail
-
p. 673 - 682
(2007/10/03)
-
- Ceric ammonium nitrate (CAN) mediated esterification of N-Boc amino acids allows either retention or removal of the N-Boc group
-
Reaction of N-Boc amino acids with ceric ammonium nitrate in an alcohol as the solvent at room temperature resulted in the esterification of N-Boc amino acids with Boc group retention. When the reaction was conducted at reflux temperature, esterification was accompanied with simultaneous removal of the Boc group. Both reactions gave the desired products in good yields.
- Kuttan, Ashani,Nowshudin, Shiek,Rao
-
p. 2663 - 2665
(2007/10/03)
-
- Synthesis and structure-activity relationship of a novel sulfone series of TNF-α converting enzyme inhibitors
-
Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1- methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl} -5-piperidinecarboxamide) with a sulfonyl group led to a new series of α,β-cyclic and β,β-cyclic γ-sulfonyl hydroxamic acids, which were potent TNF-α converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy-(4S,5S)-1-methyl-5-{[4-(2-methyl-4- quinolinylmethoxy)phenyl]sulfonylmethyl}-4-pyrrolidinecarboxamide) exhibited IC50 values of 1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP-1, -2, -9 and -13 and was orally bioavailable with an F value of 46% in mice.
- Xue, Chu-Biao,Chen, Xiao-Tao,He, Xiaohua,Roderick, John,Corbett, Ronald L.,Ghavimi, Bahman,Liu, Rui-Qin,Covington, Maryanne B.,Qian, Mingxin,Ribadeneira, Maria D.,Vaddi, Krishna,Trzaskos, James,Newton, Robert C.,Duan, James J.-W.,Decicco, Carl P.
-
p. 4453 - 4459
(2007/10/03)
-
- An efficient method to prepare α-sulfonyl hydroxamic acid derivatives
-
α-Sulfonyl hydroxamic acid derivatives are biologically important molecules. An efficient protocol has been developed to make these molecules via a direct sulfonylation of enolates. Several piperidine containing α-sulfonyl hydroxamic acid compounds have been prepared by this procedure.
- Sandanayaka, Vincent P.,Zask, Arie,Venkatesan, Aranapakam M.,Baker, Jannie
-
p. 4605 - 4607
(2007/10/03)
-
- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
-
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras
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-
-
- Tartronic acids, their acetalic ethers and O-esters
-
Tartronic acid acetalic ethers and esters of the general formula: STR1 are provided and are useful in treatment of bone dysmetabolism. As examples, Ra and Rb may be hydrogen, B is a C2 -C12 acyl group, R is phenyl and n is 0-12.
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-
-
- Inhibitors of farnesyl-protein transferase
-
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and treatment of cancer.
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-
