- FERROPORTIN INHIBITORS AND METHODS OF USE
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The subject matter described herein is directed to Ferroportin inhibitor compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis.
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Paragraph 0339; 0340
(2020/07/07)
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- COMPOSITION, COMPOSITION FOR DYNAMIC NUCLEAR POLARIZATION, POLARIZATION ENHANCING METHOD, HIGHLY POLARIZED SUBSTANCE, AND NMR MEASUREMENT METHOD
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A composition containing (1) a porous material and (2) a polarization source for dynamic nuclear polarization containing a molecule capable of being in an excited triplet state. According to the composition, a dynamic nuclear polarization system that has
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Paragraph 0164; 0165
(2020/12/14)
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- Method for synthesizing dexmedetomidine hydrochloride
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The invention belongs to the technical field of drug preparation, and particularly relates to a method for synthesizing dexmedetomidine hydrochloride. The method for synthesizing dexmedetomidine hydrochloride comprises the steps that reaction of 2,3-dimethylbenzoyl chloride and 1-N,N-dimethyl sulfonyl-2-(tert-butyldimethylsily)-5-(2,3-dimethyl benzoyl) imidazole is adopted, reflux is carried out to remove a protecting group under the action of hydrochloric acid, intermediate 4(5)-(2,3-dimethyl benzoyl) imidazole is obtained, lastly, reduction is carried out to obtain medetomidine under the action of monomethylamine, dexmedetomidine is obtained through the resolution of medetomidine under the action of tartaric acid, and lastly, dexmedetomidine is salified with hydrochloric acid to obtain dexmedetomidine hydrochloride. Compared with the prior art, the method for synthesizing dexmedetomidine hydrochloride has the advantages that a synthetic route is shorter, the operation is easy, and astarting material is easy to obtain.
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Paragraph 0028; 0029; 0030
(2019/04/26)
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- Dynamic Nuclear Polarization of Metal-Organic Frameworks Using Photoexcited Triplet Electrons
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While dynamic nuclear polarization based on photoexcited triplet electrons (triplet-DNP) has the potential to hyperpolarize nuclear spins of target substrates in the low magnetic field at room temperature, there has been no triplet-DNP system offering str
- Fujiwara, Saiya,Hosoyamada, Masanori,Tateishi, Kenichiro,Uesaka, Tomohiro,Ideta, Keiko,Kimizuka, Nobuo,Yanai, Nobuhiro
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supporting information
p. 15606 - 15610
(2018/11/23)
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- HETEROARLY AMIDES AS INHIBITORS OF PROTEIN AGGREGATION
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The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.
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Paragraph 0127
(2015/09/23)
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- SUBSTITUTED HETEROCYCLIC ACETAMIDES AS KAPPA OPIOID RECEPTOR (KOR) AGONISTS
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The present invention relates to a series of substituted compounds having the general formula (I), including their ste reoisomers and/or their pharmaceutically acceptable salts, wherein R1, R2, R3. R4, R5, and R6 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.
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Page/Page column 150
(2013/09/26)
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- Bare histidine-serine models: Implication and impact of hydrogen bonding on nucleophilicity
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A new family of 2-hydroxyalk(en/yn)ylimidazoles has been evaluated as serine-histidine bare dyad models for the ring-opening reaction of L-lacOCA, a cyclic O-carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring-opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments. A couple of reliable experimental and theoretical methods have been developed to readily monitor the strength of the intramolecular hydrogen bond in dilute solution. Results show that the folded conformers are the most nucleophilic species because of the intramolecular hydrogen bond. Copyright
- Leclaire, Julien,Mazari, Messaoud,Zhang, Yuan,Bonduelle, Colin,Thillaye Du Boullay, Olivier,Martin-Vaca, Blanca,Bourissou, Didier,De Riggi, Innocenzo,Fortrie, Rémy,Fotiadu, Frédéric,Buono, Gérard
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supporting information
p. 11301 - 11309
(2013/09/02)
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- Lead optimization of a sulfonylurea-based piperazine pyridazinone series of glucan synthase inhibitors
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The structure-activity relationship studies of a novel sulfonylurea series of piperazine pyridazine-based small molecule glucan synthase inhibitors is described. The optimization of PK profiles within the series led to the discovery of several compounds with improved pharmacokinetic profiles which demonstrated in vitro potency against clinically relevant strains. However, the advancement of compounds from this series into a non-lethal systemic fungal infection model failed to show in vivo efficacy.
- Zych, Andrew J.,Lam, Sang Q.,Jenkins, David M.,Herr, R. Jason,Ting, Pauline C.,Lee, Joe F.,Kuang, Rongze,Wu, Heping,Kim, David W.,Aslanian, Robert G.,Wainhaus, Samuel,Black, Todd A.,Cacciapuoti, Anthony,McNicholas, Paul M.,Xu, Yiming,Walker, Scott S.
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scheme or table
p. 4896 - 4899
(2012/08/13)
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- A novel method for the one-pot conversion of carboxylic acids to N,N-dimethylamides
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A simple, efficient, and new method has been developed for the preparation of N,N-dimethylamides from carboxylic acids. As described below, treatment of a variety of aromatic carboxylic acids with N,N-dimethylsulfamoyl imidazole or N,N-dimethylsulfamoyl chloride in the presence of a mixture of methanesulfonic acid/phosphorus pentoxide (2:1, v/w) proceeded effectively to afford the corresponding N,N-dimethylamides inmoderate to good yields. Thismethod is easy, rapid, and good yielding for the synthesis of N,N-dimethylamides from carboxylic acids. Iranian Chemical Society 2012.
- Kaboudin, Babak,Haghighat, Hamideh
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p. 951 - 955
(2013/02/23)
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- INHIBITORS OF POLO-LIKE KINASE
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The present invention provides compounds having a structure according to Formula (I):or a salt or solvate thereof, wherein ring A, U1, U2, U3, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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Page/Page column 260
(2012/04/23)
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- Studies toward the total synthesis of nagelamide K
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A stereocontrolled strategy toward the synthesis of nagelamide K has been developed. The dimeric imidazole acrylate, diimidazolidenesuccinate, was constructed as a synthetic precursor by a Ni-catalyzed coupling reaction; the microwave-promoted intramolecular aza-Michael addition afforded the imidazo[1,5-a]pyridine core structure of nagelamide K in high stereoselectivity. A detaurine-dediamino analogue of nagelamide K has been prepared.
- Jiang, Biao,Wang, Jue,Huang, Zuo-Gang
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scheme or table
p. 2070 - 2073
(2012/06/29)
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- PTERIDINONES AS INHIBITORS OF POLO - LIKE KINASE
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The present invention provides compounds having a structure according to Formula (I) or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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Page/Page column 129; 130
(2011/07/09)
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- IMIDAZOLYL MODULATORS OF 5-HT3 RECEPTORS
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The present invention relates to new imidazolyl modulators of 5-HT3 receptors, pharmaceutical compositions thereof, and methods of use thereof.
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- HETEROCYCLODIAZEPINE CANNABINOID RECEPTOR MODULATORS FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods useful as modulators of CB2 for the treatment or prevention of disease states including, but not limited to pain, autoimmune disease, malabsorption syndrome, pulmonary disease, osteoporosis, muscle spasm in cancer, neuromuscular disorder, and atherosclerosis progression.
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Page/Page column 28
(2009/04/24)
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- 4-Benzyl-1H-imidazoles with oxazoline termini as histamine H3 receptor agonists
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Research on the therapeutic applications of the histamine H3 receptor (H3R) has traditionally focused on antagonists/inverse agonists. In contrast, H3R agonists have received less attention despite their potential use in s
- Wijtmans, Maikel,Celanire, Sylvain,Snip, Erwin,Gillard, Michel R.,Gelens, Edith,Collart, Philippe P.,Venhuis, Bastiaan J.,Christophe, Bernard,Hulscher, Saskia,Van Der Goot, Henk,Lebon, Florence,Timmerman, Henk,Bakker, Remko A.,Lallemand, Bénédicte I. L. F.,Leurs, Rob,Talaga, Patrice E.,De Esch, Iwan J. P.
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supporting information; experimental part
p. 2944 - 2953
(2009/04/11)
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- Isoprene-catalysed lithiation: deprotection and functionalisation of imidazole derivatives
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The isoprene-catalysed lithiation of different 1-substituted imidazoles (1) (such as trityl, allyl, benzyl, vinyl, N,N-dimethylsulfamoyl, para-toluenesulfonyl, tert-butoxycarbonyl, acetyl, trimethylsilyl, tert-butyldimethylsilyl derivatives) leads to the
- Torregrosa, Rosario,Pastor, Isidro M.,Yus, Miguel
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p. 947 - 952
(2007/10/03)
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- NOVEL HETEROARYL DERIVATIVE
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A heteroaryl derivative of the formula (1): (wherein Ring Z is an optionally substituted heteroaryl, R1 is a carboxyl group or an alkoxycarbonyl group, etc., W1 and W2 are an optionally substituted lower alkylene, Ar1 is an optionally substituted arylene or an optionally substituted heteroarylene, W3 is a single bond, a lower alkylene, a lower alkenylene, etc., W4 is a single bond, -NR10-, etc., Ar2 is an optionally substituted aryl or an optionally substituted heteroaryl), or a prodrug thereof, or a pharmaceutically acceptable salt thereof.
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Page/Page column 30
(2008/06/13)
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- Extending pummerer reaction chemistry. Synthesis of (±)- dibromophakellstatin by oxidative cyclization of an imidazole derivative
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(Chemical Equation Presented) The diastereoselective oxidative cyclization of a dihydrooroidin derivative is reported. The thioimidate product formed by application of a new variant of the Pummerer reaction serves as a precursor to dibromophakellstatin.
- Feldman, Ken S.,Skoumbourdis, Amanda P.
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p. 929 - 931
(2007/10/03)
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- NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
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This invention relates to novel pyrazole derivatives of formula (I) wherein R1 to R4 are as defined in the summary and pharmaceutically acceptable salts and solvates thereof, methods to inhibits or modulate Human Immunodeficiency Virus (HIV) reverse trans
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- 4-SUBSTITUTED IMIDAZOLE-2-THIONES AND IMIDAZOL- 2-ONES AS AGONISTS OF THE ALPHA- 2B AND ALPHA-2C ADRENERGIC RECEPTORS
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Compounds of Formula (I): where X is S and the variables have the meaning defined in the specification are specific or selective to alpha2B and/or alpha2C adrenergic receptors in preference over alpha2A adrenergic receptors, and as such have no or only minimal cardivascular and/or sedatory activity. These compounds of Formula (I) are useful as medicaments in mammals, including humans, for treatment of diseases and or alleviations of conditions which are responsive to treatment by agonists of alpha2B adrenergic receptors. Compounds of Formula (I) where X is O also have the advantageous property that they have no or only minimal cardivascular and/or sedatory activity and are useful for treating pain and other conditions with no or only minimal cardivascular and/or sedatory activity.
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- Cycloheptene compounds
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Compound of formula (I): wherein: X represents a bond or alkylene, CO, S(O)n, —S(O)n—A1—, —CO—A1—, —A—S(O)n—A′1— or —A1—CO—A′1—, Y represents aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted, R1, R2, R3 and R4 each independently of the others represent hydrogen or aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted, ?or R1, R2, R3 and R4, taken in pairs, together form a bond, or form a fused benzene ring or a fused aromatic or partially unsaturated heterocycle, T represents —CH(R5)—, —N(R5)— or —N(R5)CO—, V represents hydrogen or unsubstituted or substituted aryl or heteroaryl, A2 represents [C(R6)(R′6)]p, R7 and R8 are as defined in the description, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base and medicinal products containing the same are useful as farnesyl transferase inhibitors.
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- Tetrahydronaphthyl and thiazole, oxazole or imidazole substituted ethene derivatives having retinoid-like activity, reduced skin toxicity and reduced teratogenecity
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Compounds of the formula STR1 as herein defined, have retinoid-like activity and are substantially non-teratogenic and non-irritating to the skin.
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- Synthesis of 1-(Dimethylsulfamoyl)-2- and 5-Imidazolecarboxaldehydes. Rearrangement of 1-(Dimethylsulfamoyl)-5-imidazolecarboxaldehyde to the 4-Carboxaldehyde
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Lithiation of 1-(dimethylsulfamoyl)imidazole by n-butyllithium, followed by substitution with dimethylformamide provided 1-(dimethylsulfamoyl)-2-imidazolecarboxaldehyde in 19percent yield.When 1-(dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)imidazole was lithiated by sec-butyllithium, followed by methyl formate, there was obtained 1-(dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)-5-imidazolecarboxaldehyde (57percent).Removal of the silyl group by acetic acid yielded 1-(dimethylsulfamoyl)-5-imidazolecarboxaldehyde (11, 96percent) as a gum.Isomerization of 11 took place slowly at room temperature (10 days), or faster in tetrahydrofuran solution containing triethylamine (2 hours) to form crystalline 1-(dimethylsulfamoyl)-4-imidazolecarboxaldehyde (12) in 68percent yield.Proton and carbon-13 nmr spectra were alanyzed to determine the structure of the isomers.However, only X-ray crystallography established the structure of 1-(dimethylsulfamoyl)-4-imidazolecarboxaldehyde, unequivocally.A mechanism for the isomerization of 11 to 12 is proposed.
- Kim, Jang-Woo,Abdelaal, Salma M.,Bauer, Ludwig,Heimer, Norman E.
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p. 611 - 620
(2007/10/02)
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- A simple and efficient synthesis of N-protected imidazole-4-carbaldehyde
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Successive addition of BuLi, triethylsilyl chloride, s-BuLi and DMF to 1- (N,N-dimethylsulfamoyl)imidazole (1) yields pure 1-(N,N-dimethylsulfamoyl)- 2-(triethylsilyl)imidazole-4-carbaldehyde (2) as judged by 1H NMR spectroscopy. Treatment of 2 with 2 N HCl leads to free imidazole-4- carbaldehyde (3) (overall yield 70.2%).
- Winter,Retey
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p. 245 - 246
(2007/10/02)
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- Synthesis and Anticonvulsant Activities of α-Heterocyclic α-Acetamido-N-benzylacetamide Derivatives
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Earlier studies showed that (R,S)-α-acetamido-N-benzylacetamides (2) containing a five- and six-membered aromatic or heteroaromatic group appended at the C(α) site displayed outstanding activity in the maximal electroshock-induced seizure (MES) test in mi
- Kohn, Harold,Sawhney, Kailash N.,Bardel, Patrick,Robertson, David W.,Leander, J. David
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p. 3350 - 3360
(2007/10/02)
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- 2-Protecting Groups for 5-Lithiation in the Synthesis of Imidazoles
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Various substituents have been examined as possible 2-protecting groups against organolithium reagents in the syntheses of imidazoles on the basis of the ease of decarboxylation of imidazole-2-carboxylic acids and cleavage of the C(2)-Si bond.The tertiary
- Ngochindo, Raphael I.
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p. 1645 - 1648
(2007/10/02)
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- 2,5-Dilithiation of N-Protected Imidazoles. Syntheses of 2,5-Disubstituted Derivatives of 1-Methoxymethyl-, 1-Triphenylmethyl-, and 1-(N,N-Dimethylsulphonamido)-imidazole
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The conditions previously established for the dilithiation of 1-methylimidazole are shown to be applicable to 1-methoxymethyl- and 1-triphenylmethyl-imidazole allowing good-yielding syntheses of 1,2,5-trisubstituted imidazole derivatives.The suitability of the 1-substituted (and of other groups) for the N-protection of imidazoles in dilithiation experiments is discussed and the use of the N,N-dimethylsulphamoyl protecting group is proposed. 1-Sulphamoylimidazole undergoes mono- and 2,5-di-lithiation quantitatively at low temperatures and in short reaction times.The results of work-up of the 2,5-dilithio intermediate with 1 mol equiv. of iodomethane or dimethyl sulphate indicate selectivity in favour of reaction at the 5-position.
- Chadwick, Derek J.,Ngochindo, Raphael I.
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p. 481 - 486
(2007/10/02)
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- Betylates. 1. Synthesis and reactions of an isolable betylate, N,N-dimethyl-N-(phenoxysulfonyl)methanaminium fluorosulfate
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Phenyl betylate fluorosulfate (2), the first example of a "betylate" (trialkylammoniosulfate ester), has been prepared by methylation of phenyl N,N-dimethylsulfamate with methyl fluorosulfate.Nucleophiles react with 2 either by attack on the sulfur or methyl carbon atoms, but with no sign of any products derived from benzyne or the phenyl cation.A synthesis of enol N,N-dimethylsulfamates has been devised using a reagent, Me2NSO2N(1+)Me3 FSO3(1-), prepared from tetramethylsulfamide and methyl fluorosulfate, but no satisfactory method was found for converting the sulfamic ester to the betylate.Evidence is presented that phenyl chlorosulfate reacts with trimethylamine to give the phenylbetylate which then undergoes further reaction.
- King, James Frederick,Lee, Teresa Mee-Ling
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p. 356 - 361
(2007/10/02)
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