- Diradicals Photogeneration from Chloroaryl-Substituted Carboxylic Acids
-
With the aim of generating new, thermally inaccessible diradicals, potentially able to induce a double-strand DNA cleavage, the photochemistry of a set of chloroaryl-substituted carboxylic acids in polar media was investigated. The photoheterolytic cleavage of the Ar?Cl bond occurred in each case to form the corresponding triplet phenyl cations. Under basic conditions, the photorelease of the chloride anion was accompanied by an intramolecular electron-transfer from the carboxylate group to the aromatic radical cationic site to give a diradical species. This latter intermediate could then undergo CO2 loss in a structure-dependent fashion, according to the stability of the resulting diradical, or abstract a hydrogen atom from the medium. In aqueous environment at physiological pH (pH=7.3), both a phenyl cation and a diradical chemistry was observed. The mechanistic scenario and the role of the various intermediates (aryl cations and diradicals) involved in the process was supported by computational analysis.
- Di Terlizzi, Lorenzo,Protti, Stefano,Ravelli, Davide,Fagnoni, Maurizio
-
-
- Rational design of cannabinoid type-1 receptor allosteric modulators: Org27569 and PSNCBAM-1 hybrids
-
Allosteric modulation offers an alternate approach to target the cannabinoid type-1 receptor (CB1) for therapeutic benefits. Examination of the two widely studied prototypic CB1 negative allosteric modulators (NAMs) Org27569 and PSNCBAM-1 revealed structural resemblance and similar structure–activity relationships (SARs). In silico docking and dynamics simulation studies using the crystal structure of CB1 co-bound with CP55,940 and Org27569 suggested that Org27569 and PSNCBAM-1 occupied the same binding pocket and several common interactions were present in both series with the CB1 receptor. A new scaffold was therefore designed by merging the key structural features from the two series and the hybrids retained these binding features in the in silico docking studies. In addition, one such hybrid displayed similar functions to Org27569 in dynamic simulations by preserving a key R2143.50-D3386.30 salt bridge and maintaining an antagonist-like Helix3-Helix6 interhelical distance. Based on these results, a series of hybrids were synthesized and assessed in calcium mobilization, [35S]GTPγS binding and cAMP assays. Several compounds displayed comparable potencies to Org27569 and PSNCBAM-1 in these assays. This work offers new insight of the SAR requirement at the allosteric site of the CB1 receptor and provides a new scaffold that can be optimized for the development of future CB1 allosteric modulators.
- Nguyen, Thuy,Gamage, Thomas F.,Decker, Ann M.,Finlay, David B.,Langston, Tiffany L.,Barrus, Daniel,Glass, Michelle,Harris, Danni L.,Zhang, Yanan
-
-
- SUBSTITUTED, SATURATED AND UNSATURATED N-HETEROCYCLIC CARBOXAMIDES AND RELATED COMPOUNDS FOR THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
-
The invention provides substituted, saturated and unsaturated N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.
- -
-
Paragraph 00485
(2021/04/01)
-
- COMPOUNDS FOR SENSING REACTIVE OXYGEN SPECIES AND METHODS FOR USING THE SAME
-
Provided herein according to some embodiments of the invention are aryl boronate and/or aryl diaminoboryl compounds. Also provided are methods of detecting the presence of hydrogen peroxide (H2O2) and/or other reactive oxygen species (ROS) in a cell and/or tissue by contacting the cell and/or tissue with aryl boronate and/or aryl diaminoboryl compounds. Also provided according to embodiments of the invention are methods of producing persulfides in the presence of hydrogen peroxide (H2O2) and/or other reactive oxygen species (ROS) in a cell and/or tissue by contacting the cell and/or tissue with aryl boronate and/or aryl diaminoboryl compounds.
- -
-
Page/Page column 25
(2022/01/04)
-
- Mechanism of 8-Aminoquinoline-Directed Ni-Catalyzed C(sp3)-H Functionalization: Paramagnetic Ni(II) Species and the Deleterious Effect of Carbonate as a Base
-
Studies into the mechanism of 8-aminoquinoline-directed nickel-catalyzed C(sp3)-H arylation with iodoarenes were carried out, to determine the catalyst resting state and optimize catalytic performance. Paramagnetic complexes undergo the key C-H activation step. The ubiquitous base Na2CO3is found to hinder catalysis; replacement of Na2CO3with NaOtBu gave improved catalytic turnovers under milder conditions. Deprotonation of the 8-aminoquinoline derivativeN-(quinolin-8-yl)pivalamide (1a) at the amide nitrogen using NaH, followed by reaction with NiCl2(PPh3)2allowed for the isolation of complex Ni([AQpiv]-κN,N)2(3) with chelating N-donors (where [AQpiv] = C9NH6NCOtBu). Complex3is a four-coordinate disphenoidal high-spin Ni(II) complex, excluding short anagostic Ni-tBu hydrogen interactions. Complex3reacts with the paddle-wheel [Ph3PNi(μ-CO2tBu)2]2(6·PPh3) ortBuCO2H to give insoluble {[AQpiv]Ni(O2CtBu)}2(5). Dissolution of5in donor solvents L (L= DMSO and DMF) gave a paramagnetic intermediate assigned by NMR as [AQpiv]Ni(O2CtBu)L (5·L) and equilibrium reformation of3and6·L. DFT calculations support this equilibrium in solution. Both3and5undergo C-H activation at temperatures as low as 80 °C and in the presence of PR3(PR3= PPh3, PiBu3) to give Ni(C9NH6NCOCMe2CH2-κN,N,C)PR3(7·PR3). The C-H functionalization reaction orders with respect to7·PiBu3, iodoarenes, and phosphines were determined. Hammett analysis using electronically different aryl iodides suggests a concerted oxidative addition mechanism for the C-H functionalization step; DFT calculations were also carried out to support this finding. When Na2CO3is used as the base, the rate determination step for C-H functionalization appears to be 8-aminoquinoline deprotonation and binding to Ni. The carbonate anion was also observed to provide a deleterious NMR-inactive low-energy off-cycle resting state in catalysis. Replacement of Na2CO3with NaOtBu improved catalysis at milder conditions and made carboxylic acid and phosphine additives unnecessary. Complex3and its functionalized analogues were observed as the catalyst resting state under these conditions.
- Liu, Junyang,Johnson, Samuel A.
-
supporting information
p. 2970 - 2982
(2021/06/28)
-
- UREA DERIVATIVES AS CB1 ALLOSTERIC MODULATORS
-
Heteroaryl and aliphatic analogs of diarylurea-based cannabinoid 1 receptor (CB1 R) allosteric modulators of formula (I) are described. Exemplary analogs can provide improved potencies and pharmacokinetic properties. Methods of using the analogs to treat
- -
-
Page/Page column 78-79
(2021/01/23)
-
- An Innovative Hydrogen Peroxide-Sensing Scaffold and Insight Towards its Potential as an ROS-Activated Persulfide Donor
-
Reactive sulfur species, such as hydrogen sulfide, persulfides, and polysulfides, have recently emerged as key signaling molecules and important physiological mediators within mammalian systems. To better assess the therapeutic potential of their exogenou
- Green, Nolan M.,Hankins, Rynne A.,Harty, Megan N.,Kalk, Madison A.,Lukesh, John C.,Suarez, S. Israel
-
supporting information
p. 22238 - 22245
(2020/10/12)
-
- Harnessing Applied Potential: Selective β-Hydrocarboxylation of Substituted Olefins
-
The construction of carboxylic acid compounds in a selective fashion from low value materials such as alkenes remains a long-standing challenge to synthetic chemists. In particular, β-addition to styrenes is underdeveloped. Herein we report a new electrosynthetic approach to the selective hydrocarboxylation of alkenes that overcomes the limitations of current transition metal and photochemical approaches. The reported method allows unprecedented direct access to carboxylic acids derived from β,β-trisubstituted alkenes, in a highly regioselective manner.
- Alkayal, Anas,Buckley, Benjamin R.,Malkov, Andrei V.,Montanaro, Stephanie,Tabas, Volodymyr,Wright, Iain A.
-
supporting information
(2020/02/13)
-
- Palladium-catalyzed 2-pyridylmethyl-directed β-C(sp3)–H activation and cyclization of aliphatic amides with gem-dibromoolefins: A rapid access to γ-lactams
-
The direct Pd-catalyzed β-C(sp3)–H activation and cyclization of aliphatic amides bearing a removable 2-pyridylmethyl directing group with gem-dibromoolefins is described for the first time to construct a variety of γ-lactams. The resulting products with Z- and E-configurations can be easily separated and purified after the reaction, demonstrating the effectiveness and applicability of the method herein developed.
- Zhou, Danni,Wang, Chunxia,Li, Mingliang,Long, Zheng,Lan, Jingbo
-
supporting information
p. 191 - 193
(2017/11/17)
-
- Decarboxylative Giese-Type Reaction of Carboxylic Acids Promoted by Visible Light: A Sustainable and Photoredox-Neutral Protocol
-
We describe herein a transition-metal-free method for the decarboxylative generation of radicals from carboxylic acids and their 1,4-addition to Michael acceptors. The Fukuzumi catalyst (9-mesitylene-10-methylacridinium perchlorate, [Acr-Mes]ClO4) enabled this transformation under visible-light irradiation at room temperature with CO2 as the only byproduct. The scope and limitations of this protocol were examined by using a range of Michael acceptors (15 examples) and carboxylic acids (18 examples). The use of 3-hydroxypivalic acid in this protocol allowed the straightforward formation of a diastereomerically pure δ-lactone. Moreover, when a homoallylic acid was used, a radical cascade reaction took place with the formation of three C–C bonds.
- Ramirez, Nieves P.,Gonzalez-Gomez, Jose C.
-
supporting information
p. 2154 - 2163
(2017/04/24)
-
- Nickel-catalysed direct alkylation of thiophenes via double C(sp3)-H/C(sp2)-H bond cleavage: The importance of KH2PO4
-
A Ni-catalyzed oxidative C-H/C-H cross-dehydrogenative coupling (CDC) reaction was developed for constructing various highly functionalized alkyl (aryl)-substituted thiophenes. This method employs thiophenes and aliphatic (aromatic) amides that contain an 8-aminoquinoline as a removable directing group in the presence of a silver oxidant. The approach enables the facile one-step synthesis of substituted thiophenes with high functional group compatibility via double C-H bond cleavage without affecting C-Br and C-I bonds. DFT calculations verify the importance of KH2PO4 as an additive for promoting C-H bond cleavage and support the involvement of a Ni(iii) species in the reaction.
- Wang, Xie,Xie, Peipei,Qiu, Renhua,Zhu, Longzhi,Liu, Ting,Li, You,Iwasaki, Takanori,Au, Chak-Tong,Xu, Xinhua,Xia, Yuanzhi,Yin, Shuang-Feng,Kambe, Nobuaki
-
supporting information
p. 8316 - 8319
(2017/07/26)
-
- Styrene-acrylic acid synthetic method of the compound
-
The invention discloses a method for directly achieving direct arylation reaction of benzene and carbonyl beta-bite sp3C-H bonds employing palladium acetate as a catalyst under the action of bidentate guide base, so as to synthesize a phenylpropionic acid compound. The method comprises the following steps: sequentially adding a 2-propionamido-pyridine-1-oxide, palladium acetate, gibbsite dipotassium phosphate, an aryl iodide compound and dimethylsulfoxide to a shrek tube in an air atmosphere, and reacting for 20-30 hours; after the reaction is ended, cooling to a room temperature, extracting, drying, concentrating and carrying out chromatographic separation to obtain an arylated product; dissolving the obtained arylated product into an ethanol solution of NaOH and reacting for 20-30 hours; and after reaction is ended, neutralizing, extracting, drying, concentrating and carrying out column chromatography to obtain the phenylpropionic acid compound. The method is mild in reaction condition, and good in functional group tolerance; an external additive is not needed; and the carbonyl beta-bite sp3C-H bonds in the 2-propionyl aminopyridine-1-oxide can be directly arylated.
- -
-
Paragraph 0030; 0039; 0044; 0045
(2017/05/02)
-
- Sterically Demanding Oxidative Amidation of α-Substituted Malononitriles with Amines Using O2
-
An efficient amidation method between readily available 1,1-dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of α-peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile α-carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles.
- Li, Jing,Lear, Martin J.,Hayashi, Yujiro
-
supporting information
p. 9060 - 9064
(2016/07/26)
-
- A C-H Insertion Approach to Functionalized Cyclopentenones
-
Cyclopentenones are synthetically versatile structures, and their straightforward construction from alkynone substrates by employing synthetically streamlining C-H insertion is conceptually appealing and of high synthetic potential. But, its implementation is very limited. Herein we report a Au-catalyzed version, which affords 2-bromocyclopent-2-en-1-ones with a broad scope and synthetically desirable diastereoselectivities. The proposed key intermediate capable of the observed insertion into unactivated C-H bonds is a fully functionalized gold vinylidene, which is generated via a novel intermolecular strategy. This flexible access of likely gold vinylidenes opens various opportunities to explore their versatile reactivities.
- Wang, Youliang,Zarca, Maxence,Gong, Liu-Zhu,Zhang, Liming
-
supporting information
p. 7516 - 7519
(2016/07/06)
-
- Nickel-Catalyzed Addition-Type Alkenylation of Unactivated, Aliphatic C-H Bonds with Alkynes: A Concise Route to Polysubstituted γ-Butyrolactones
-
(Chemical Equation Presented). Through the nickel-catalyzed chelation-assisted C-H bond activation strategy, the addition-type alkenylation of unreactive β-C(sp3)-H bonds of aliphatic amides with internal alkynes is developed for the first time to produce γ,δ-unsaturated carboxylic amide derivatives. The resulting alkenylated products can further be transformed into polysubstituted γ-butyrolactones with pyridinium chlorochromate (PCC).
- Li, Mingliang,Yang, Yudong,Zhou, Danni,Wan, Danyang,You, Jingsong
-
supporting information
p. 2546 - 2549
(2015/05/27)
-
- Hydrodecarboxylation of Carboxylic and Malonic Acid Derivatives via Organic Photoredox Catalysis: Substrate Scope and Mechanistic Insight
-
A direct, catalytic hydrodecarboxylation of primary, secondary, and tertiary carboxylic acids is reported. The catalytic system consists of a Fukuzumi acridinium photooxidant with phenyldisulfide acting as a redox-active cocatalyst. Substoichiometric quantities of Hünigs base are used to reveal the carboxylate. Use of trifluoroethanol as a solvent allowed for significant improvements in substrate compatibilities, as the method reported is not limited to carboxylic acids bearing α heteroatoms or phenyl substitution. This method has been applied to the direct double decarboxylation of malonic acid derivatives, which allows for the convenient use of dimethyl malonate as a methylene synthon. Kinetic analysis of the reaction is presented showing a lack of a kinetic isotope effect when generating deuterothiophenol in situ as a hydrogen atom donor. Further kinetic analysis demonstrated first-order kinetics with respect to the carboxylate, while the reaction is zero-order in acridinium catalyst, consistent with another finding suggesting the reaction is light limiting and carboxylate oxidation is likely turnover limiting. Stern-Volmer analysis was carried out in order to determine the efficiency for the carboxylates to quench the acridinium excited state.
- Griffin, Jeremy D.,Zeller, Mary A.,Nicewicz, David A.
-
supporting information
p. 11340 - 11348
(2015/09/21)
-
- Method for producing hematopoietic stem cells using pyrazole compounds
-
An expanding agent for hematopoietic stem cells and/or hematopoietic progenitor cells useful as a therapy for various hematopoietic diseases and useful for improvement in the efficiency of gene transfer into hematopoietic stem cells for gene therapy is provided. A method of producing hematopoietic stem cells and/or hematopoietic progenitor cells, which comprises expanding hematopoietic stem cells by culturing hematopoietic stem cells ex vivo in the presence of a compound represented by the formula following (I), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof (wherein R1 to R8 are as defined in the description).
- -
-
Page/Page column 173; 174
(2016/01/10)
-
- Mechanistic study of silver-catalyzed decarboxylative fluorination
-
The silver-catalyzed fluorination of aliphatic carboxylic acids by Selectfluor in acetone/water provides access to fluorinated compounds under mild and straightforward reaction conditions. Although this reaction provides efficient access to fluorinated alkanes from a pool of starting materials that are ubiquitous in nature, little is known about the details of the reaction mechanism. We report spectroscopic and kinetic studies on the role of the individual reaction components in decarboxylative fluorination. The studies presented herein provide evidence that Ag(II) is the intermediate oxidant in the reaction. In the rate-limiting step of the reaction, Ag(I)-carboxylate is oxidized to Ag(II) by Selectfluor. Substrate inhibition of the process occurs through the formation of a silver-carboxylate. Water is critical for solubilizing reaction components and ligates to Ag(I) under the reaction conditions. The use of donor ligands on Ag(I) provides evidence of oxidation to Ag(II) by Selectfluor. The use of sodium persulfate as an additive in the reaction as well as NFSI as a fluorine source further supports the generation of a Ag(II) intermediate; this data will enable the development of a more efficient set of reaction conditions for the fluorination.
- Patel, Niki R.,Flowers, Robert A.
-
p. 5834 - 5841
(2015/06/16)
-
- β-Arylation of carboxamides via iron-catalyzed C(sp3)-H bond activation
-
A 2,2-disubstituted propionamide bearing an 8-aminoquinolinyl group as the amide moiety can be arylated at the β-methyl position with an organozinc reagent in the presence of an organic oxidant, a catalytic amount of an iron salt, and a biphosphine ligand at 50 C. Various features of selectivity and reactivity suggest the formation of an organometallic intermediate via rate-determining C-H bond cleavage rather than a free-radical-type reaction pathway.
- Shang, Rui,Ilies, Laurean,Matsumoto, Arimasa,Nakamura, Eiichi
-
supporting information
p. 6030 - 6032,3
(2013/05/22)
-
- PYRAZOLE COMPOUNDS HAVING THERAPEUTIC EFFECT ON MULTIPLE MYELOMA
-
Novel therapeutic agents for myeloma are provided. A therapeutic agent for multiple myeloma containing a pyrazole compound represented by the formula (1): wherein R1 is C1-C6 alkyl, C1-C6 alkyl substituted with R17, C1-C6 haloalkyl, phenyl, phenyl substituted with a R11's or the like, R2 is a hydrogen atom, C1-C6 alkyl, phenyl or phenyl optionally substituted with e R21's or the like, R3 is a hydrogen atom or the like, X is a single bond or —(CR6, R7)n—, each of R4 and R5 is independently C1-C6 alkyl or the like, R6 and R7 are hydrogen atoms or C1-C6 alkyl, R8 is phenyl, phenyl optionally substituted with k R81's or the like, a tautomer of the compound or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient.
- -
-
Paragraph 0217; 0218
(2013/10/07)
-
- Pd(II)-catalyzed primary-C(sp3)-H acyloxylation at room temperature
-
With the aid of a novel S-methyl-S-2-pyridyl-sulfoximine (MPyS) directing group (DG), the unactivated primary β-C(sp3)-H bond of MPyS-N-amides oxidizes at room temperature. The catalytic conditions are applicable to the diacetoxylation of primary β,β′-C(sp 3)-H bonds, and the carboxylic acid solvent is pivotal in the formation of the C-O bond. The MPyS-DG cleaves from the oxidation products and is recovered. This method provides convenient access to α,α′- disubstituted-β-hydroxycarboxylic acids.
- Rit, Raja K.,Yadav, M. Ramu,Sahoo, Akhila K.
-
supporting information; experimental part
p. 3724 - 3727
(2012/08/28)
-
- Nickel(0)/NaHMDS adduct-mediated intramolecular alkylation of unactivated arenes via a homolytic aromatic substitution mechanism
-
A variety of polycycles can be synthesized via an intramolecular alkylation cyclization promoted by Ni(PPh3)4 and NaHMDS. Mechanistic investigations support the catalytic nature of Ni0 in the course of TEMPO scavenging experiments and its association with the substrate and NaHMDS to form an adduct by DOSY NMR.
- Beaulieu, Louis-Philippe B.,Roman, Daniela Sustac,Vallee, Frederic,Charette, Andre B.
-
supporting information; experimental part
p. 8249 - 8251
(2012/09/07)
-
- Highly regioselective carbonylation of unactivated C(sp3)-H bonds by ruthenium carbonyl
-
The regioselective carbonylation of unactivated C(sp3)-H bonds of aliphatic amides was achieved using Ru3(CO)12 as a catalyst. The presence of a 2-pyridinylmethylamine moiety in the amide is crucial for a successful reaction. The reaction shows a preference for C-H bonds of methyl groups as opposed to methylene C-H bonds and tolerates a variety of functional groups. The stoichiometric reaction of an amide with Ru 3(CO)12 gave a dinuclear ruthenium complex in which the 2-pyridinylmethylamino moiety was coordinated to the ruthenium center in an N,N manner.
- Hasegawa, Nao,Charra, Valentine,Inoue, Satoshi,Fukumoto, Yoshiya,Chatani, Naoto
-
supporting information; experimental part
p. 8070 - 8073
(2011/07/08)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to 6-(4-pyι?midinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
Page/Page column 157-158
(2010/07/10)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
Page/Page column 114-115
(2010/11/04)
-
- Indium-catalyzed coupling reaction between silyl enolates and alkyl chlorides or alkyl ethers
-
The coupling reactions of alkyl chlorides with silyl enolates catalyzed by InBr3, and the coupling reactions of alkyl ethers with silyl enolates catalyzed by the combined Lewis acid of InBr3/Me3SiBr are described. In both reaction systems, various types of silyl enolates were used to give corresponding α-alkylated esters, ketones, carboxylic acids, amides, thioesters, and aldehydes.
- Nishimoto, Yoshihiro,Saito, Takahiro,Yasuda, Makoto,Baba, Akio
-
experimental part
p. 5462 - 5471
(2009/12/01)
-
- UREA COMPOUNDS AS GAMMA SECRETASE MODULATORS
-
The present invention provides compounds Formula (I) that are gamma secretase modulators and are therefore useful for the treatment of diseases treatable by modulation of gamma secretase such as Alzheimer's disease. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
- -
-
Page/Page column 70
(2010/01/29)
-
- Palladium-catalyzed methylation and arylation of sp2 and sp 3 C-H bonds in simple carboxylic acids
-
The use of preformed sodium carboxylates as substrates led to the first observation of facile Pd-insertions into sp3 β-C-H bonds in simple aliphatic acids. Consequently, Pd-catalyzed methylation and arylation of o-C-H bonds in benzoic acids and β-C-H bonds in aliphatic acids using either a phenylboronate, methylboronic acid, or ArI have been achieved via a C-H activation/C-C coupling sequence. Copyright
- Giri, Ramesh,Maugel, Nathan,Li, Jiao-Jie,Wang, Dong-Hui,Breazzano, Steven P.,Saunders, Lindsey B.,Yu, Jin-Quan
-
p. 3510 - 3511
(2007/10/03)
-
- Pyrazolopyrimidines as therapeutic agents
-
The present invention is directed to pyrazolopyrimidine derivatives of formula (I) wherein the substituents are defined herein, which are useful as kinase inhibitors and as such are useful for affecting angiogenesis and diseases and conditions associated with angiogenesis.
- -
-
-
- [1,3] Sigmatropic rearrangement of ketene silyl acetals derived from benzyl α-substituted propanoates
-
A novel [1,3] sigmatropic rearrangement of ketene silyl acetals derived from benzyl α-substituted propanoates is developed. The reaction of ketene silyl acetal derived from optically active 1-phenylethyl 2-methylpropanoate mainly proceeds with the retenti
- Shiina, Isamu,Nagasue, Hiroshi
-
p. 5837 - 5840
(2007/10/03)
-
- Pyrazolopyrimidines as therapeutic agents
-
The present invention provides compounds of Formula I, including pharmaceutically acceptable salts and/or prodrugs thereof, where G, R2, and R3 are defined as described herein.
- -
-
-
- RETROVIRAL PROTEASE INHIBITORS
-
Urea-containing hydroxyethylamine peptide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
- -
-
-
- 13C magnetic resonance studies. 144.1 An examination of β-enolization in the bicyclo[3.3.1]-and [3.2.2]nonan-2-one system
-
While 3, 3-dimethylbicyclo[3.3. l]nonan-2-one (5) is stable under strongly basic conditions (/-BuCT//-BuOH/185°C), its isomer, 3, 3-dimethylbicyclo[3. 2.2]nonan-2-one (6), is slowly transformed to 5. Similarly, 3, 3-dimethylbicyclo-[3.2.2]non-6-en-2-one (
- Muir, David J.,Stothers
-
p. 1099 - 1105
(2007/10/02)
-
- Nitrogen Participation in the Deacylation of D-Glucosamine and α-Chymotrypsin Derivatives. Explanation of the Stereospecificity of Acyl-α-Chymotrypsin Hydrolysis
-
The hydrolysis of ethyl 3,4,6-tri-O-acetyl-2-deoxy-2-amino-β-D-glucopyranoside and acylated α-chymotrypsins has been investigated.Both transformations are catalyzed by neighbouring nitrogen atom participation.The stereospecificity of acylated enzyme hydrolysis can be explained by the specific steric hindrance of nitrogen participation.Keywords: selective deacylation, stereospezific ester hydrolysis, acylated derivatives of α-chymotrypsin, 2-amino-2-deoxy-glucose
- Oetvoes, Laszlo,Kraicsovits, Ferenc
-
p. 5009 - 5014
(2007/10/02)
-
- Cephalosporin derivatives
-
Cephemcarboxylic acid esters of the general formula STR1 pharmaceutical preparations which are active against bacterial infections, which contain such cephem derivatives, a process for the preparation of the cephem derivatives and the pharmaceutical preparations, and also the use of the cephem derivatives for combating bacterial infections.
- -
-
-
- Rates and Mechanism for the Solvolyses of 2,2-Dimethyl-2-sila-1-indanyl Bromide and α-Trialkylsilylbenzyl p-Toluenesulfonates. α-Silicon Effect on the Stability of Benzylic Cations in Solution
-
α-Silicon effect on the benzylic solvolysis has been investigated.The solvolysis of 2,2-dimethyl-2-sila-1-indanyl bromide in aq acetone exhibits a linear response to the solvent ionizing power YBr, with a slope m close to unity (m = 0.93) and g
- Shimizu, Nobujiro,Osajima, Erika,Tsuno, Yuho
-
p. 1145 - 1152
(2007/10/02)
-
- A Facile Method for Synthesis of Three Carbon-Homologated Carboxylic Acid by Regioselective Ring-opening of β-Propiolactones with Organocopper Reagents
-
Organocopper reagents, such as diorganocuprates, organocopper-tributylphosphine, and Grignard reagents in the presence of a copper (I) salt, reacted with β-propiolactones by regioselective β-carbon-oxygen fission to give 3-substituted propionic acids.Among these three kinds of organocopper reagents, diorganocuprate, especially halomagnesium cuprate gave the highest yields of the acids, which was remarkably observed in the ring-opening of sterically hindered β-propiolactones such as β-methyl- and α,β-dimethyl-β-propiolactones and also in the reactions using the organocopper reagents with vinyl and allyl substituents.The ring-opening of β-propiolactone was confirmed to proceed by SN2 pathway with predominant inversion of configuration of the β-carbon by using the reaction of cis-α,β-dimethyl-β-propiolactone with di-tert-butylcuprate to afford syn-2,3,4,4-tetramethylpentanoic acid.
- Kawashima, Masatoshi,Sato, Toshio,Fujisawa, Tamotsu
-
p. 403 - 412
(2007/10/02)
-
- Antihypercholesterolemic compounds
-
Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors which are useful as antihypercholesterolemic agents and are represented by the following general structural formulae (I) and (II): STR1 and pharmaceutically acceptable salts of the
- -
-
-
- A THREE CARBON HOMOLOGATION BY THE RING-OPENING OF β-PROPIOLACTONES WITH DIORGANOCUPRATES
-
Various organocuprates react with β-propiolactones to give β-substituted propionic acids in high yields.
- Fujisawa, Tamotsu,Sato, Toshio,Kawara, Tatsuo,Kawashima, Masatoshi
-
p. 2181 - 2184
(2007/10/02)
-
- Competitive - and -Sigmatropic Rearrangements
-
Several cases of the oxy-Cope rearrangement, which typically prefers the -sigmatropic route, are now known to occur in a -sigmatropic fashion.By contrast, the symmetry-allowed thermal rearrangement of carbanions (or their enol derivatives; e.g.,
- Arnold, Richard T.,Kulenovic, Srdanka T.
-
p. 891 - 894
(2007/10/02)
-
- COPPER-CATALYZED REACTION OF GRIGNARD REAGENTS WITH β-PROPIOLACTONES: A CONVENIENT METHOD FOR THE SYNTHESIS OF Β-SUBSTITUTED PROPIONIC ACIDS
-
Grignard reagents react with β-propiolactones in the presence of a copper(I) catalyst to give β-substituted propionic acids in high yields.
- Sato, Toshio,Kawara, Tatsuo,Kawashima, Masatoshi,Fujisawa, Tamotsu
-
p. 571 - 574
(2007/10/02)
-
- Indaneacetic acid derivatives
-
This invention provides new compounds of formula I, STR1 wherein R1 is lower alkyl, R2 is hydrogen or lower alkyl, R3 is hydrogen or lower alkyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, chlorine or lower alkyl, and each of R6 and R7 is hydrogen, or, when R5 is hydrogen, R6 may also be chlorine or lower alkyl, and R7 chlorine or lower alkyl, Useful as anti-phlogistic and anti-arthritic agents.
- -
-
-
- 13,14-Didehydro-PGA1 compounds
-
This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.
- -
-
-
- 2,2-Difluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGE2 compounds
-
This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.
- -
-
-
- Cis-13-PGF2α analogs
-
This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is of the cis configuration. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.
- -
-
-
- 13,14-Didehydro-PG3 compounds
-
This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.
- -
-
-
- 13,14-Didehydro-PG analogs
-
This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.
- -
-
-
- 9-Deoxy-PGF2 Analogs
-
Prostaglandin analogs with the following cyclopentane ring structure: STR1 are disclosed along with intermediates useful in their preparation and processes for their preparation. These analogs are useful for some of the same pharmacological purposes as the prostaglandins.
- -
-
-
- 4,4,5,5-Tetradehydro-PGE1 analogs
-
This invention comprises certain analogs of the prostaglandins in which there is a triple bond between C-5 and C-6 or C-4 and C-5. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.
- -
-
-
- Aliphatic 2-decarboxy-2-hydroxymethyl-13,14-didehydro-PG compounds
-
This invention comprises certain analogs of the prostaglandins in which the C-1 carboxyl is replaced by a primary alcohol and the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.
- -
-
-