- Mechanized silica nanoparticles based on reversible bistable [2]pseudorotaxanes as supramolecular nanovalves for multistage pH-controlled release
-
Cucurbit[6]uril-based reversible bistable [2]pseudorotaxanes were designed, synthesized and installed on the surface of mesoporous silica nanoparticles as supramolecular nanovalves. The assembled mechanized silica nanoparticles realize the multistage pH-controlled release of benzotriazole and the potential for reutilization.
- Wang, Mingdong,Chen, Tao,Ding, Chendi,Fu, Jiajun
-
-
Read Online
- A facile and versatile electro-reductive system for hydrodefunctionalization under ambient conditions
-
A general electrochemical system for reductive hydrodefunctionalization is described, employing the inexpensive and easily available triethylamine (Et3N) as a sacrificial reductant. This protocol is characterized by facile operation, sustainable conditions, and exceptionally wide substrate scope covering the cleavage of C-halogen, N-S, N-C, O-S, O-C, C-C and C-N bonds. Notably, the selectivity and capability of reduction can be conveniently switched by simple incorporation or removal of an alcohol as a co-solvent.
- Huang, Binbin,Guo, Lin,Xia, Wujiong
-
supporting information
p. 2095 - 2103
(2021/03/26)
-
- ARYL SULFONAMIDES AS SMALL MOLECULE STAT3 INHIBITORS
-
The present disclosure provides pharmaceutical compositions comprising aryl sulfonamide Stat3 small molecule inhibitors and certain pharmaceutically acceptable salts thereof, and methods of their use for treating cancer.
- -
-
Paragraph 00467; 00468
(2021/01/29)
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- HTT MODULATORS FOR TREATING HUNTINGTON'S DISEASE
-
Provided herein are certain compounds useful as HTT modulators. Such compound are useful in the treatment of Huntington's disease.
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Page/Page column 336
(2021/11/20)
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- 18F-LABELLED COMPOUND FOR PROSTATE CANCER DIAGNOSIS, AND USE THEREOF
-
The present invention relates to an 18F-labelled compound, and a use thereof. The compound selectively binds to a prostate-specific membrane antigen (PSMA), and enables the acquisition of clear prostate cancer images in a short time when used in positron
- -
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Paragraph 0037-0038
(2020/05/30)
-
- A Greener Approach for the Chemoselective Boc Protection of Amines Using Sulfonated Reduced Graphene Oxide as a Catalyst in Metal- And Solvent-Free Conditions
-
Sulfonated reduced graphene oxide (SrGO) has displayed great potential as a solid acid catalyst due to its efficiency, cost-effectiveness, and reliability. In this study, SrGO was synthesized by the introduction of sulfonic acid-containing aryl radicals onto chemically reduced graphene oxide using ultrasonication. The SrGO catalyst was characterized by Fourier Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM). Further, SrGO was effectively utilized as a metal-free and reusable solid acid catalyst for the chemoselective N - t -Boc protection of various aromatic and aliphatic amines under solvent-free conditions. The N - t -Boc protection of amines was easily achieved under ambient conditions affording high yields (84-95percent) in very short reaction times (5 min-2 h). The authenticity of the approach was confirmed by a crystal structure. The catalyst could be easily recovered and was reused up to seven consecutive catalytic cycles without any substantial loss in its activity.
- Awasthi, Satish K.,Mishra, Anupam,Mittal, Rupali
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p. 591 - 601
(2020/02/13)
-
- Larotinib derivative and preparation method and application thereof
-
The invention relates to a larotinib derivative and a preparation method and application thereof, and provides a novel larotinib derivative with anti-tumor activity. The novel larotinib derivative isbeneficial to improving the anti-tumor activity of the l
- -
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Paragraph 0071-0072; 0081
(2020/09/16)
-
- Focal adhesion kinase inhibitor and use
-
The invention belongs to the field of medicines, relates to a focal adhesion kinase inhibitor and use, in particular relates to a novel focal adhesion kinase inhibitor compound, or stereoisomers, geometric isomers, tautomers, oxynitrides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, further relates to the use of the compound and pharmaceutical compositions as medicines, in particular the use of the compound and pharmaceutical compositions in manufacture of medicines for treatment or prevention of cancer, pulmonary hypertension, and pathological angiogenesis-related diseases.
- -
-
Paragraph 0663; 0665; 0666
(2019/01/08)
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- Design, synthesis and structure-activity relationship study of novel naphthoindolizine and indolizinoquinoline-5,12-dione derivatives as IDO1 inhibitors
-
Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as a promising target for cancer immunotherapy. Many naphthoquinone derivatives have been reported as IDO1 inhibitors so far. Herein, two series of naphthoquinone derivatives, naphthoindolizine and indolizinoquinoline-5,12-dione derivatives, were synthesized and evaluated for their IDO1 inhibitory activity. Most of the target compounds showed significant inhibition potency and high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). The structure-activity relationship was also summarized. The most potent compounds 5c (IC50 23 nM, IDO1 enzyme), and 5b′ (IC50 372 nM, HeLa cell) were identified as promising lead compounds.
- Yang, Rui,Chen, Yu,Pan, Liangkun,Yang, Yanyan,Zheng, Qiang,Hu, Yue,Wang, Yuxi,Zhang, Liangren,Sun, Yang,Li, Zhongjun,Meng, Xiangbao
-
supporting information
p. 4886 - 4897
(2018/09/11)
-
- One-pot synthesis of primary amines from carboxylic acids through rearrangement of in situ generated hydroxamic acid derivatives
-
A one-pot synthesis of primary amines from carboxylic acids through a Lossen rearrangement of hydroxamic acid derivatives, which were in situ generated by the reaction of carboxylic acids with O-trimethylsilylhydroxylamine (NH2OTMS) and carbonyl diimidazole (CDI, 1.5 equiv) in dimethyl sulfoxide at room temperature, has been achieved. This one-pot method could be applied to various carboxylic acids such as aromatic, heteroaromatic, aliphatic, and optically active substrates.
- Hoshino, Yujiro,Ohtsuka, Naoya,Okada, Takuya,Honda, Kiyoshi
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p. 5304 - 5307
(2016/11/16)
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- Design, synthesis, and evaluation of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives as Aurora kinase inhibitors
-
A series of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives were designed, synthesized, and evaluated for the Aurora kinase inhibitory activities. The novel hinge-binder tethered 1,2,3-triazolylsalicylamide scaffold was effectively assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). A variety of alkynes with hinge binders were used to search proper structures-binding relationship to the hinge region. The synthesized 1,2,3-triazolylsalicylamide derivatives showed significant Aurora kinase inhibitory activity. In particular, 8a inhibited Aurora A kinase with an IC50 value of 0.284 μM, whereas 8m inhibited Aurora B kinase with an IC50 value of 0.364 μM.
- Jeong, Yunkyung,Lee, Jooyeon,Ryu, Jae-Sang
-
supporting information
p. 2114 - 2124
(2016/04/20)
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- Azaquinazoline Inhibitors Of Atypical Protein Kinase C
-
The present application provides a compound of formula (I) and/or a salt thereof, wherein R1, G, and X are as defined herein. A compound of formula (I) and/or its salts have aPKC inhibitory activity, and may be used to treat proliferative disor
- -
-
Paragraph 0325
(2015/12/24)
-
- METALLOENZYME INHIBITOR COMPOUNDS
-
The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
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Page/Page column 123-124
(2014/08/07)
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- Zinc chloride promoted efficient and facile BOC protection of amines
-
Amines are efficiently protected as their BOC derivatives under mild reaction conditions when reacted with BOC anhydride in presence of ZnCl2. The present method is applicable to a variety of amines including aliphatic, aromatic as well as heteroaromatic amines. This protocol appears to be competitive and in some cases superior to previously reported procedures that work under basic conditions.
- Arifuddin, M.,Lakshmikant, N.,Rajasekar, N.,Shinde, D. B.
-
p. 1168 - 1172,5
(2020/08/31)
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- Microwave assisted mild, rapid, solvent-less, and catalyst-free chemoselective N-tert-butyloxycarbonylation of amines
-
Microwave assisted simple, rapid, solventless, and catalyst-free chemoselective method for the protection of amino group in aromatic, aliphatic, heterocyclic, aralkyl amines, phenyl hydrazine, and amino acid esters in good to excellent isolated yield (83-98%) in short reaction time (2-12 min) has been reported.
- Dighe, Satish N.,Jadhav, Hemant R.
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p. 5803 - 5806
(2012/10/29)
-
- Nonsolvent application of ionic liquids: Organo-catalysis by 1-alkyl-3-methylimidazolium cation based room-temperature ionic liquids for chemoselective N-tert-butyloxycarbonylation of amines and the influence of the C-2 hydrogen on catalytic efficiency
-
1-Alkyl-3-methylimidazolium cation based ionic liquids efficiently catalyze N-tert-butyloxycarbonylation of amines with excellent chemoselectivity. The catalytic role of the ionic liquid is envisaged as "electrophilic activation" of di-tert-butyl dicarbonate (Boc2O) through bifurcated hydrogen bond formation with the C-2 hydrogen of the 1-alkyl-3-methylimidazolium cation and has been supported by a downfield shift of the imidazolium C-2 hydrogen of 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][NTf2]) from δ 8.39 to 8.66 in the presence of Boc2O in the 1H NMR and a drastic reduction of the catalytic efficiency with 1-butyl-2,3-dimethylimidazolium ionic liquids that are devoid of the C-2 hydrogen. The differential time required for reaction with aromatic and aliphatic amines has offered means for selective N-t-Boc formation during inter and intramolecular competitions. Preferential N-t-Boc formation with secondary aliphatic amine has been achieved in the presence of primary aliphatic amine. Comparison of the catalytic efficiency for N-t-Boc formation with a common substrate revealed that [bmim][NTf2] is superior to the reported Lewis acid catalysts.
- Sarkar, Anirban,Roy, Sudipta Raha,Parikh, Naisargee,Chakraborti, Asit K.
-
experimental part
p. 7132 - 7140
(2011/10/08)
-
- Guanidine hydrochloride as an organocatalyst for N-Boc protection of amino groups
-
A simple and efficient method for the chemoselective N-Boc protection of the amine moiety in a variety of compounds is described using di-tert-butyl dicarbonate and guanidine hydrochloride as an organocatalyst in ethanol at 35-40°C. Selective mono-N-Boc protection of diamines and chemoselective protection of hydroxylamines without formation of any side products is achieved. Amino acids and peptides are N-Boc protected efficiently in excellent yields under convenient reaction conditions.
- Jahani, Fatemeh,Tajbakhsh, Mahmood,Golchoubian, Hamid,Khaksar, Samad
-
supporting information; experimental part
p. 1260 - 1264
(2011/04/15)
-
- An efficient and highly chemoselective N-Boc protection of amines, amino acids, and peptides under heterogeneous conditions
-
A simple and efficient procedure for chemoselective mono-N-Boc protection of various structurally diverse amines, amino acids, and peptides with di-tert-butyl dicarbonate using Amberlyst-15 as catalyst in ethanol is described. The catalyst can be readily separated from the reaction products with simple filtration and recovered for direct reuse. No competitive side-reactions such as formation of isocyanate, urea, oxazolidinone, and N,N-di-Boc derivatives were observed.
- Jahani, Fatemeh,Tajbakhsh, Mahmood,Khaksar, Samad,Azizi, Mohamad Reza
-
experimental part
p. 1035 - 1043
(2012/07/27)
-
- Ferric chloride-promoted efficient and facile BOC protection of amines
-
Amines are efficiently protected as their tertiary butyloxycarbonyl (BOC) derivatives under mild reaction condition when reacted with (BOC)2O in the presence of FeCl3. The present method is applicable to a variety of amines including aliphatic, aromatic, and hetero aromatic amines.
- Tasneem,Rajanna
-
body text
p. 715 - 719
(2011/04/12)
-
- PEG-mediated facile protocol for N-Boc protection of amines
-
We have reported an efficient and eco-friendly protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)2O in the presence of PEG-400 at room temperature. The reaction gave excellent
- Siddaiah,Basha,Padma Rao,Viplava Prasad,Suryachendra Rao
-
experimental part
p. 1127 - 1129
(2011/02/28)
-
- Antibacterial Agents
-
Naphthalene, quinoline, quinoaline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 14
(2008/12/07)
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- Efficient, solventless N-Boc protection of amines carried out at room temperature using sulfamic acid as recyclable catalyst
-
A simple, rapid, and efficient protocol for the chemoselective N-Boc protection of amines using sulfamic acid as catalyst is described. N-Boc protection of various structurally diverse aliphatic, aromatic, alicyclic, and heterocyclic amines (1°, 2°, 3°) was carried out with (Boc)2O using sulfamic acid as catalyst (5 mol %) at room temperature under solventless conditions. The advantages of this method are simplicity, shorter reaction times (1-15 min), a cost-effective catalyst, and excellent isolated yields (90-100%); it is also environmentally benign. Moreover, the combined use of ultrasound and sulfamic acid achieves a synergic effect that is especially marked in the N-Boc protection of deactivated (sterically hindered and electron-deficient) amines. The catalyst possesses distinct advantages: ease of handling, cleaner reactions, high activity, and excellent chemoselectivity.
- Upadhyaya, Dharita J.,Barge, Alessandro,Stefania, Rachele,Cravotto, Giancarlo
-
p. 8318 - 8322
(2008/04/13)
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- DOSAGE OF 4-AMINOPYRIDINE DERIVATIVES FOR TREATMENT OF CENTRAL NERVOUS SYSTEM INJURIES
-
The invention provides novel pyridines, pharmaceutical compositions comprising such pyridines, and the use of such compositions in treating injured mammalian nerve tissue, including but not limited to an injured spinal cord, in one embodiment, the compounds, compositions, and methods of the instant invention treat a mammalian nerve tissue injury by restoring action potential or nerve impulse conduction through a nerve tissue lesion. Significantly,in vivo application of compounds of the instant invention established, on the basis of SSEP testing, that the compounds provide longer lasting effects at lower concentrations than comparable treatment with the known agent 4-aminopyridine (4 AP).Λ''invention concerne de nouvelles pyridines, des compositions pharmaceutiques comprenant ces pyridines et l''utilisation de ces compositions dans le traitement des lésions du tissu nerveux mammifère, y compris mais non de fa?on limitative, une lésion de la moelle épinière. Dans un mode de réalisation, les composés, les compositions et les méthodes selon l''invention traitent une lésion du tissu nerveux mammifère en rétablissant le potentiel d''action ou la conduction nerveuse à travers une lésion du tissu nerveux. De manière significative, l''application in vivo de composés selon l''invention établit, sur la base d''un test de potentiel évoqué somesthésique, que les composés produisent à de faibles concentrations des effets plus durables qu''un traitement comparable à l''aide de l''agent 4-aminopyridine (4 AP) connu.
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Page/Page column 12
(2008/06/13)
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- Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature
-
Commercially available copper(II) tetrafluoroborate hydrate was found to be a highly efficient catalyst for chemoselective N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions and at room temperature. Various aromatic amines were protected as their N-tert-butyl carbamates in high yields and in short times. No competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation was observed. Chemoselective N-tert-butoxycarbonylation was achieved with substrates bearing OH and SH groups. Chiral α-amino acid esters afforded the corresponding N-t-Boc derivatives in excellent yields.
- Chankeshwara, Sunay V.,Chakraborti, Asit K.
-
p. 1087 - 1091
(2007/10/03)
-
- HClO4-SiO2 as a new, highly efficient, inexpensive and reusable catalyst for N-tert-butoxycarbonylation of amines
-
Perchloric acid adsorbed on silica-gel (HClO4-SiO2) was found to be a new, highly efficient, inexpensive and reusable catalyst for chemoselective N-tert-butoxycarbonylation of amines at room temperature and under solvent-free conditions. The Royal Society of Chemistry 2006.
- Chakraborti, Asit K.,Chankeshwara, Sunay V.
-
p. 2769 - 2771
(2008/03/28)
-
- Indium(III) halides as new and highly efficient catalysts for N-tert-butoxycarbonylation of amines
-
Indium(III) bromide and chloride efficiently catalysed the N-tert-butoxycarbonylation of amines with (Boc)2O at room temperature and under solvent-free conditions. Various aromatic, heteroaromatic and aliphatic amines were converted to N-tert-butylcarbamates in excellent yields in short times. Chiral amines, esters of α-amino acids and β-amino alcohols afforded optically pure N-t-Boc derivatives in high yields. The reactions were chemoselective and no competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation were observed. Chemoselective conversion to N-tert-butylcarbamates took place with amino alcohols without any formation of oxazolidinones. Georg Thieme Verlag Stuttgart.
- Chankeshwara, Sunay V.,Chakraborti, Asit K.
-
p. 2784 - 2788
(2008/02/05)
-
- Catalyst-free chemoselective N-tert-butyloxycarbonylation of amines in water
-
Catalyst-free N-tert-butyloxycarbonylation of amines in water is reported. The N-t-Boc derivatives were formed chemoselectively without any isocyanate, urea, N,N-di-t-Boc, and O/S-t-Boc as side products. Chiral amines, esters of α-amino acids, and β-amino alcohol afforded optically pure N-t-Boc derivatives. Amino alcohol and 2-aminophenol afforded the N-t-Boc derivative without oxazolidinone formation. Selectivity was observed during competition of aromatic amine vs aliphatic amine, amine vs amino acid ester, amine vs amino alcohol, and primary amine vs secondary amine.
- Chankeshwara, Sunay V.,Chakraborti, Asit K.
-
p. 3259 - 3262
(2007/10/03)
-
- DIPHENYL OX-INDOL-2-ON COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER
-
The present invention relates to substituted 3,3-diphenyl-1,3-dihydro-indol-2-one compounds, and the use of such compounds for the preparation of a medicament for the treatment of cancer in a mammal. It is postulated that treatment of cancers in which inh
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Page/Page column 36
(2010/02/14)
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- Development of novel 4-aminopyridine derivatives as potential treatments for neurological injury and disease
-
The amine position of the K+ channel blocker 4-aminopyridine was functionalized to form amide, carbamate and urea derivatives in an attempt to identify novel compounds which restore conduction in injured spinal cord. Eight derivatives were tested in vitro, using a double sucrose gap chamber, for the ability to restore conduction in isolated, injured guinea pig spinal cord. The methyl, ethyl and t-butyl carbamates of 4-aminopyridine induced an increase in the post injury compound action potential. The methyl and ethyl carbamates were further tested in an in vivo model of spinal cord injury. These results represent the first time that 4-aminopyridine has been derivatized without losing its ability to restore function in injured spinal cord tissue.
- Smith, Daniel T.,Shi, Riyi,Borgens, Richard B.,McBride, Jennifer M.,Jackson, Kevin,Byrn, Stephen R.
-
p. 908 - 917
(2007/10/03)
-
- SUBSTITUTED NAPHTHYRIDINE DERIVATIVES AS INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR AND THEIR USE IN THE TREATMENT OF HUMAN DISEASES
-
Inhibitors of MIF having a naphthyridine backbone are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: (Ia), (Ib), (Ic), (Id) including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R, R1, R2, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.
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Page/Page column 124; 207-208
(2010/02/11)
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- ANTITHROMBOTIC AROMATIC ETHERS
-
This application relates to a compound of formula (I) (or a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa and/or thrombin, as well as a process for its preparation and intermediates therefor.
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Page/Page column 105-106
(2008/06/13)
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- SUBSTITUTED AZACHINAZOLINES HAVING AN ANTIVIRAL ACTION
-
The invention relates to substituted azachinazolines and methods for the production thereof. The invention also relates to the use of said azachinazolines for producing medicaments for the treatment and/or prophylaxis of diseases, especially for using as antiviral agents, especially against cytomegaloviruses.
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Page/Page column 20
(2008/06/13)
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- PYRROLOPYRIDINE DERIVATIVES AND USE THEREOF FOR TREATING DISEASES MEDIATED BY PROSTAGLANDIN D2 (PGD2)
-
Compounds of formula (Ia) or (Ib): or pharmaceutically acceptable salts, hydrates, solvates, complexes or prodrugs thereof are useful in the treatment of allergic diseases such as asthma, allergic rhinitis and atopic dermatitis.
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Page/Page column 13; 20
(2010/02/15)
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- DIAMINE DERIVATIVES
-
A compound represented by formula (1):Q1-Q2-To-N(R1) -Q3-N(R2)-T1-Q4 [wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 represents the following group: (wherein Q5 is an alkylene group having 1 to 8 carbon atoms, or the like); and T0 and T1 are carbonyl groups or the like], a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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Page/Page column 70
(2008/06/13)
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- Diamine derivatives
-
A compound represented by the general formula (1): Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4??(1) wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a group in which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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-
-
- NOVEL ETHYLENEDIAMINE DERIVATIVES
-
A compound represented by the following formula (1):Q-Q-T-N(R)-Q-N(R)-T-Q [wherein, R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may have a substituent, or the like; Q2 is a single bond or the like; Q3 represents the following group: -C(R3a)(R4a)-{C(R3b)(R4b)}m1-{C(R3c)(R4c)}m2-{C(R3d)(R4d)}m3-{C(R3e)(R4e)}m4-C(R3f)(R4f)- (in which, R3a to R4e represent hydrogen or the like); T0 represents a carbonyl group or the like; and T1 represents -COCONR- or the like]; or salt thereof, solvate thereof, or N-oxide thereof. The compound is useful as a preventive and/or therapeutic agent for cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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Page/Page column 67
(2010/02/14)
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- PYRROLOPYRIDINE-2-CARBOXYLIC ACID AMIDE INHIBITORS OF GLYCOGEN PHOSHORYLASE
-
Compounds represented by Formula (I): or pharmaceutically acceptable salts thereof, are inhibitors of glycogen phosphorylase and are useful in the prophylactic or therapeutic treatment of diabetes, hyperglycemia, hypercholesterolemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis or tissue ischemia e.g. myocardial ischemia, and as cardioprotectants.
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-
- Synthesis of 2-quinolones via palladium-catalyzed carbonylative annulation of internal alkynes by N-substituted o-iodoanilines
-
The palladium-catalyzed annulation of internal alkynes by N-substituted o-iodoanilines under 1 atm of carbon monoxide results in the formation of 3,4-disubstituted 2-quinolones. The nature of the substituent on the nitrogen is crucial to obtaining high yields of 2-quinolones. The best results are obtained using alkoxycarbonyl, p-tolylsulfonyl, and trifluoroacetyl substituents. The nitrogen substituent is lost during the course of the reaction resulting in the formation of N-unsubstituted 2-quinolones. A variety of internal alkynes, bearing alkyl, aryl, heteroaryl, hydroxyl, and alkoxyl substituents, are effective in this process. Electron-rich and electron-poor N-substituted o-iodoanilines, as well as heterocyclic analogues, can be employed as annulating agents.
- Kadnikov, Dmitry V.,Larock, Richard C.
-
p. 6772 - 6780
(2007/10/03)
-
- HETEROCYCLIC KINASE INHIBITORS
-
Compounds having the formula (I) are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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-
-
- DIAMINE DERIVATIVES
-
A compound represented by the general formula (1):Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4 wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a group in which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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-
-
- SUBSTITUTED (AMINOIMINOMETHYL OR AMINOMETHYL) BENZOHETEROARYL COMPOUNDS
-
This invention is directed to an (aminoiminomethyl or aminomethyl) benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.
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-
- Generation of ligand conformations in continuum solvent consistent with protein active site topology: Application to thrombin
-
Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code 1UVT) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based
- Greenidge, Paulette A.,Mérette, Sandrine A. M.,Beck, Richard,Dodson, Guy,Goodwin, Christopher A.,Scully, Michael F.,Spencer, John,Weiser, J?rg,Deadman, John J.
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p. 1293 - 1305
(2007/10/03)
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- ETHYLENEDIAMINE DERIVATIVES
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The invention relates a compound represented by the formula (1):Q1-Q2-C(=O)-N(R1)-Q3-N(R2)-T1-Q4 wherein R1 and R2 represent H or the like; Q1 represents an aromatic ring, heterocyclic ring or the like; Q2 represents a single bond, aromatic ring, heterocyclic ring or the like; Q3 represents a group or the like, Q4 represents an aromatic ring, heterocyclic ring or the like; and T1 represents -CO- or -SO2-, and a medicine which comprises the compound and is useful for thrombosis and embolism.
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- HETEROAROMATIC AMIDES AS INHIBITOR OF FACTOR XA
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This application relates to heteroaromatic amides (or a pharmaceutically acceptable salt thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.
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- Selective nitrolytic deprotection of N-BOC-amines and N-BOC-amino acids derivatives
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The extension of the deprotection procedure using HNO3 in CH2Cl2 to a number of appropriately selected N-BOC-masked amines and derivatives of natural amino acids was investigated. The method was found to work effectively with almost all tested substrates, with the exception of activated aromatic amines and heterocycles which underwent unavoidable faster oxidation. Alanine, phenylalanine, serine and lysine derivatives were efficiently deprotected, as well as dipeptide Ala-Phe, preserving the configuration of the substrates and without affecting copresent Z and ester functions, with a remarkable selectivity towards acid sensitive t-butyl esters. The obtained amino acids esters, isolated and characterized in the form of nitrates salts, proved to be suitable intermediates to be used in peptide synthesis.
- Strazzolini, Paolo,Melloni, Tiziana,Giumanini, Angelo G
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p. 9033 - 9043
(2007/10/03)
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- Configurationally Stable Biaryl Analogues of 4-(Dimethylamino)pyridine: A Novel Class of Chiral Nucleophilic Catalysts
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A short synthetic approach toward a novel class of chiral nucleophilic catalysts, the dissymmetry of which stems from restricted rotation about an Ar-Ar bond, has been developed. The key steps of the synthesis include preparation of a nucleophilic 1-methyl-2-pyrrolino[3,2-c]pyridine core 16 by ortho-lithiation and creation of the biaryl axes via Suzuki cross-coupling reactions. Comparative HPLC studies of racemization for configurationally labile biaryls 31, 38, and 43 containing 1-methyl-2-pyrrolino[3,2-c]pyridine, 4-(dimethylamino)pyridine, and 4-(1-pyrrolidino)pyridine cores, respectively, have demonstrated that a pyrrolidino substituent ortho to the biaryl axis is optimal for slowing Ar-Ar rotation. Biaryls containing all three cores have been shown to retain DMAP-like catalytic activity in the acylation of a hindered alcohol. Biaryls 55 and 56, which are configurationally stable at ambient temperature, have also been prepared via modification of configurationally labile derivatives. Compounds 55 and 56 in optically pure form should provide a useful starting point for studies on catalytic asymmetric acyl transfer using atropisomeric analogues of DMAP.
- Spivey, Alan C.,Fekner, Tomasz,Spey, Sharon E.,Adams, Harry
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p. 9430 - 9443
(2007/10/03)
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- Synthesis of atropisomeric analogues of DMAP
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A method for the preparation of 7-aryl derivatives of N-methyl-5- azaindolinee involving Suzuki cross-coupling is described. Certain biaryls prepared in this manner exhibit atropisomerism. In particular, azaindoline 11 is shown to be configurationally sta
- Spivey, Alan C.,Fekner, Tomasz,Adams, Harry
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p. 8919 - 8922
(2007/10/03)
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- A Simple Method for the Protection of Aryl Amines as their t-Butylcarbamoyl (Boc) Derivatives
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It has been found that aryl amines can be directly protected as their Boc derivatives by treatment of the amine with two equivalents of NaHMDS in THF followed by one equivalent of di-t-butyldicarbonate.This procedure works on a wide variety of both electron-rich and electron-deficient aryl amines.
- Kelly, Terence A.,McNeil, Daniel W.
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p. 9003 - 9006
(2007/10/02)
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- Inhibitors of Cyclic AMP Phosphodiesterase. 3. Synthesis and Biological Evaluation of Pyrido and Imidazolyl Analogues of 1,2,3,5-Tetrahydro-2-oxoimidazoquinazoline
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Hybridization of structural elements of 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline ring system common to the cyclic AMP (cAMP) phosphodiesterase (PDE) inhibitors lixazinone (RS-82856,1) and anagrelide (3) with complementary features of other PDE inhibitor cardiotonic agents prompted the design and synthesis of the title compounds 7a-d, 11, 12, and 13a,b.The necessary features of these compounds were determined within the framework of the proposed active-site models for the high affinity form of cAMP PDE inhibited by cGMP (type IV).Evaluation of these targets, both in vitro as inhibitors of platelet or cardiac type IV PDE or in vivo as inotropic agents in the pentobarbital-anesthetized dog model of congestive heart failure, showed that these structure possessed negligibly enhanced activities over the parent heterocyclic system, and remained significantly inferior to 1 in all respects.This difference is ascribed to the absence of the N-cyclohexyl-N-methylbutyramidyl-4-oxy side chain of 1.The proposal that the acidic lactam-type functionality, common to the type IV PDE inhibitor inotropic agents such as 4-6 and 8-10, mimics the polarizable cyclic phosphate moiety of cAMP suggested that the side chain of 1 may function as an effective surrogate for selected characteristics of the adenine portion of cAMP.However, the results of this study show that incorporation of adenine-like hydrogen-bonding functionalities common to other type IV PDE inhibitors into the 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline system did not enhance activity to the levels observed for 1 analogues.These observations, coupled with the kinetic pattern of inhibition of type IV PDE observed for 1 and analogues, suggest that access to a secondary, lipophilic-tolerant binding site, possibly coincident with the adenine binding domain, and adjacent to the catalytic ribose-phosphate binding site of platelet and cardiac type IV PDE, is responsible for the increased potency of these compounds.
- Venuti, Michael C.,Stephenson, Robert A.,Alvarez, Robert,Bruno, John J.,Strosberg, Arthur M.
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p. 2136 - 2145
(2007/10/02)
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