- Fluorinated Sulfinates as Source of Alkyl Radicals in the Photo-Enantiocontrolled β-Functionalization of Enals
-
The generation of sulfonyl radicals has long been known as a flexible strategy in a wide range of different sulfonylative transformations. Meanwhile their use in alkylation processes has been somehow limited due to their inherent difficulty in evolving to less-stable radicals after sulfur dioxide extrusion. Herein we report a convenient strategy that involves gem-difluorinated sulfinates as an “upgrading-mask”, allowing these precursors to decompose into their corresponding alkyl radicals. The electron–donor character of sulfinates in the formation of an electron donor–acceptor (EDA) complex with transient iminium ions is displayed, achieving the first example of a stereocontrolled light-driven insertion of gem-difluoro derivatives into unsaturated aldehydes. This methodology is compatible with flow conditions, maintaining identical levels of enantiocontrol.
- Alemán, José,Rodríguez, Ricardo I.,Sicignano, Marina
-
supporting information
(2022/01/22)
-
- TGF-beta receptor inhibitor
-
The invention provides a compound shown as a formula (I) and a pharmaceutical composition thereof. The compound shown as the formula (I) of the present invention is useful as a TGF-beta receptor inhibitor, particularly a TGF beta RI inhibitor, for example, in the prevention or treatment of various TGF beta RI (ALK5) mediated related diseases.
- -
-
Paragraph 0075-0077
(2021/04/28)
-
- Derivatives of Napabucasin and pharmaceutical application thereof
-
The invention relates to derivatives of Napabucasin, and a pharmaceutical application thereof. The structure of the derivatives conforms to the general formula (I), and the water solubility of most of the compounds is obviously higher than that of Napabucasin. The compounds and pharmaceutically acceptable salts thereof can be used for preparing antitumor drugs, and the cell inhibition activity of most of the compounds is obviously superior to that of Napabucasin. Meanwhile, experiments show that the compounds have extremely high helicobacter pylori and fungal activity resistance and can be used for preparing drugs for resisting helicobacter pylori and fungal infection.
- -
-
Paragraph 0028-0029; 0031; 0033-0035
(2021/08/07)
-
- Decarboxylative Borylation of mCPBA-Activated Aliphatic Acids
-
A decarboxylative borylation of aliphatic acids for the synthesis of a variety of alkylboronates has been developed by mixing m-chloroperoxybenzoic acid (mCPBA)-activated fatty acids with bis(catecholato)diboron in N,N-dimethylformamide (DMF) at room temperature. A radical chain process is involved in the reaction which initiates from the B-B bond homolysis followed by the radical transfer from the boron atom to the carbon atom with subsequent decarboxylation and borylation.
- Wei, Dian,Liu, Tu-Ming,Zhou, Bo,Han, Bing
-
supporting information
p. 234 - 238
(2020/01/02)
-
- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
-
A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
-
supporting information
p. 5242 - 5247
(2020/02/28)
-
- Electrochemical [4+2] Annulation-Rearrangement-Aromatization of Styrenes: Synthesis of Naphthalene Derivatives
-
We report the first electrochemical strategy to synthesize functionalized naphthalene derivatives through [4+2] annulation—rearrangement–aromatization from styrenes under mild conditions. The electrolysis does not require metals, oxidants and high valence substrates, indicating the atom and step-economy ideals. The dehydrodimer produced through [4+2] cycloaddition of 4-methoxy α-methyl styrene is isolated and proved to be the key intermediate for the following oxydehydrogenation to form carbon cation, which undergoes rearrangement–aromatization to afford the final products. This reaction represents a powerful access to construct multi-substituted naphthalene blocks in a single step.
- Ma, Yueyue,Lv, Jufeng,Liu, Chengyu,Yao, Xiantong,Yan, Guoming,Yu, Wei,Ye, Jinxing
-
supporting information
p. 6756 - 6760
(2019/04/17)
-
- Nickel-Catalyzed Decarboxylative Alkenylation of Anhydrides with Vinyl Triflates or Halides
-
Decarboxylative cross-coupling of aliphatic acid anhydrides with vinyl triflates or halides was accomplished via nickel catalysis. This methodology works well with a broad array of substrates and features abundant functional group tolerance. Notably, our approach addresses the issue of safe and environmental installation of methyl or ethyl group into molecular scaffolds. The method possesses high chemoselectivity toward alkyl groups when aliphatic/aromatic mixed anhydrides are involved. Furthermore, diverse ketones could be modified with our strategy.
- Chen, Hui,Sun, Shuhao,Liao, Xuebin
-
supporting information
p. 3625 - 3630
(2019/05/24)
-
- HEPATITIS B CORE PROTEIN MODULATORS
-
The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound of formula:
- -
-
Page/Page column 160
(2018/04/13)
-
- Visible Light-Mediated Decarboxylative Alkylation of Pharmaceutically Relevant Heterocycles
-
A net redox-neutral method for the decarboxylative alkylation of heteroarenes using photoredox catalysis is reported. Additionally, this method features the use of simple, commercially available carboxylic acid derivatives as alkylating agents, enabling the facile alkylation of a variety of biologically relevant heterocyclic scaffolds under mild conditions.
- Sun, Alexandra C.,McClain, Edward J.,Beatty, Joel W.,Stephenson, Corey R. J.
-
supporting information
p. 3487 - 3490
(2018/06/26)
-
- COMPOUNDS USEFUL AS IMMUNOMODULATORS
-
The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.
- -
-
Page/Page column 62-63
(2018/07/29)
-
- TRICYCLIC COMPOUND FOR BROMODOMAIN-CONTAINING PROTEIN INHIBITOR AND PREPARATION, PHARMACEUTICAL COMPOSITION, AND APPLICATION THEREOF
-
The present applicationpresent application relates to a compound represented by Formula (III) or a pharmaceutically acceptable salt, solvent compound, active metabolite, crystal polymorph, ester, isomer, or prodrug thereof. The application further provides a pharmaceutical composition comprising the compound represented by Formula (III) and a use thereof for preparing a bromodomain inhibitor for preventing or treating various diseases, such as inflammation and cancer, related to the bromodomain.
- -
-
Paragraph 0168; 0169
(2019/01/04)
-
- HETERO-HALO INHIBITORS OF HISTONE DEACETYLASE
-
This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula I, II or any of Compounds 100-128 or any of those in Tables 2 or 3) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.
- -
-
Paragraph 257
(2017/01/26)
-
- Sulfonamide derivative and application thereof in pharmacy
-
The invention relates to a sulfonamide derivative and a pharmaceutical composition containing the same, and an application of the sulfonamide derivative and the pharmaceutical composition of the sulfonamide derivative in drug preparation, specifically the application in drug preparation of a BCL-2 family protein antagonist and the application in treatment of cancers.
- -
-
Paragraph 0248; 0249
(2017/05/02)
-
- Photoinduced, Copper-Catalyzed Decarboxylative C-N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement
-
The Curtius rearrangement is a classic, powerful method for converting carboxylic acids into protected amines, but its widespread use is impeded by safety issues (the need to handle azides). We have developed an alternative to the Curtius rearrangement that employs a copper catalyst in combination with blue-LED irradiation to achieve the decarboxylative coupling of aliphatic carboxylic acid derivatives (specifically, readily available N-hydroxyphthalimide esters) to afford protected amines under mild conditions. This C-N bond-forming process is compatible with a wide array of functional groups, including an alcohol, aldehyde, epoxide, indole, nitroalkane, and sulfide. Control reactions and mechanistic studies are consistent with the hypothesis that copper species are engaged in both the photochemistry and the key bond-forming step, which occurs through out-of-cage coupling of an alkyl radical.
- Zhao, Wei,Wurz, Ryan P.,Peters, Jonas C.,Fu, Gregory C.
-
supporting information
p. 12153 - 12156
(2017/09/12)
-
- N-Heterocyclic Carbene Ligand-Enabled C(sp3)-H Arylation of Piperidine and Tetrahydropyran Derivatives
-
PdII-catalyzed C(sp3)-H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N-heterocyclic carbene (NHC) ligand. A C(sp3)-H insertion step by the PdII/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC-mediated Pd0/PdII catalytic manifold does not operate in this reaction. This transformation provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems. PdII-catalyzed C(sp3)-H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N-heterocyclic carbene (NHC) ligand. A C-H insertion step by the PdII/NHC complex in the absence of ArI is demonstrated experimentally for the first time. This arylation method provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems (see scheme).
- Ye, Shengqing,Yang, Weibo,Coon, Timothy,Fanning, Dewey,Neubert, Tim,Stamos, Dean,Yu, Jin-Quan
-
supporting information
p. 4748 - 4752
(2016/04/05)
-
- Novel bi-cyclic or tri-cyclic heterocyclic compound
-
The present invention provides novel bi-cyclic or tri-cyclic compound represented by formula (I) or pharmaceutical acceptable salt thereof, [wherein, ring A is an aromatic group which may be substituted, one of X1 and X2 is a carbon atom, and another is a nitrogen atom, X3 is a nitrogen atom or CR2, X4 is a nitrogen atom or CR3, X5 is a sulfur atom or -CH=CH-, Z1 is an oxygen atom, -C(R6)(R7)-, -NH-, -C(R6)(R7)-NH-, -NH-C(R6)(R7)-, -C(R6)(R7)-O-, -O-C(R6)(R7)- or a single bone, one of Z2 and Z3 is CH and another one is a nitrogen atom, or both are nitrogen atoms, the other symbols are same as those defined in the specification.]
- -
-
Paragraph 3273 - 3275
(2016/10/07)
-
- Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp3 C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems
-
An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp3 C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp3)-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities. The stereochemistry of the products obtained in this work were unambiguously assigned on the basis of the X-ray structure analyses of representative compounds 3b, 3e, 4p, and 7.
- Parella, Ramarao,Babu, Srinivasarao Arulananda
-
p. 2339 - 2355
(2015/06/01)
-
- COMBINATIONS OF HEPATITIS C VIRUS INHIBITORS
-
The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.
- -
-
Page/Page column 609
(2015/02/02)
-
- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
-
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
- -
-
Paragraph 0337
(2015/08/03)
-
- HEXAHYDROPYRROLOTHIAZINE COMPOUNDS
-
A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R9 are as defined in the specification and which compound has an Αβ production inhibitory effect and may be useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Αβ and typified by Alzheimer-type dementia (AD) or Down's syndrome.
- -
-
Page/Page column 100
(2014/02/15)
-
- Simple sulfinate synthesis enables C-H trifluoromethylcyclopropanation
-
A simple method to convert readily available carboxylic acids into sulfinate salts by employing an interrupted Barton decarboxylation reaction is reported. A medicinally oriented panel of ten new sulfinate reagents was created using this method, including a key trifluoromethylcyclopropanation reagent, TFCS-Na. The reactivity of six of these salts towards C-H functionalization was field-tested using several different classes of heterocycles.
- Gianatassio, Ryan,Kawamura, Shuhei,Eprile, Cecil L,Foo, Klement,Ge, Jason,Baran, Phil S.,Burns, Aaron C.,Collins, Michael R.
-
supporting information
p. 9851 - 9855,5
(2014/10/15)
-
- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
-
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
- -
-
Paragraph 00106
(2014/10/04)
-
- INDAZOLE COMPOUNDS AS KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
-
The present teaching provide indazole compounds represented by Structural Formulae (I) or (I') or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof as protein kinase inhibitors, such as T
- -
-
Page/Page column 124
(2013/04/25)
-
- CYCLIC AMIDE DERIVATIVE
-
Provided is a compound represented by formula (1) or a pharmacologically acceptable salt thereof. (In the formula, A is C6-10 arylene, etc.; R1a, R1b and R1c each independently is a hydrogen atom, a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, etc.; R2 is an optionally substituted C6-10 aryl group, an optionally substituted 5- to 12-membered monocyclic or polycyclic heteroaryl group, an optionally substituted C7-16 aralkyl group, etc.; m is 0, etc.; n is an integer of 0 to 2.)
- -
-
Paragraph 0298; 0299; 0300
(2013/07/25)
-
- BENZAMIDE COMPOUND
-
[Problem] A compound which is useful as a GK activator is provided. [Means for Solution] The present inventors have conducted studies on compounds having a GK activating action, which are promising as active ingredients of pharmaceutical compositions for
- -
-
Page/Page column 27
(2012/11/06)
-
- Ligand-enabled methylene C(sp3)-H bond activation with a Pd(II) catalyst
-
Pd(II) insertion into β-methylene C(sp3)-H bonds was enabled by a mutually repulsive and electron-rich quinoline ligand. Ligand tuning led to the development of a method that allows for installation of an aryl group on a range of acyclic and cyclic amides containing β-methylene C(sp3)-H bonds.
- Wasa, Masayuki,Chan, Kelvin S. L.,Zhang, Xing-Guo,He, Jian,Miura, Masanori,Yu, Jin-Quan
-
supporting information
p. 18570 - 18572
(2013/01/15)
-
- 2-OXO-2- (2-PHENYL-5,6,7,8-TETRAHYDRO-INDOLIZIN-3-YL) -ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ANTIFUNGAL AGENTS
-
The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof: wherein: R1, R2, R3, R4, R5, R6, R7, R8, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
- -
-
Page/Page column 14
(2011/02/15)
-
- Compounds Which Modulate The CB2 Receptor
-
Compounds of formula (I) are disclosed. Compounds according to the and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.
- -
-
Page/Page column 14
(2010/02/17)
-
- P38 MAP KINASE INHIBITORS
-
The present disclosure relates to compounds of formula (I): which are inhibitors of p38 mitogen-activated protein kinase enzymes,particularly the alpha and gamma kinase sub-types thereof, and their use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, such as COPD
- -
-
Page/Page column 41
(2010/07/02)
-
- Modulation on C- and N-terminal moieties of a series of potent and selective linear tachykinin NK2 receptor antagonists
-
Herein we describe the synthesis of a series of new potent tachykinin NK2 receptor antagonists by the modulation of the Cand N-terminal moieties of ibodutant (MEN 15596, 1). The Nterminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C-terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK2 receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK2 receptor. Selected compounds were tested in vivo confirming their activity as NK2 antagonists. In particular, after both iv and id administration to guinea pig, compound 61b was able to antagonize NK2-induced colonic contractions with a potency and duration-of-action fully comparable to the reference compound 1 (MEN 15596, ibodutant).
- Gensini, Martina,Altamura, Maria,Dimoulas, Tula,Fedi, Valentina,Giannotti, Danilo,Giuliani, Sandro,Guidi, Antonio,Harmat, Nicholas J. S.,Meini, Stefania,Nannicini, Rossano,Pasqui, Franco,Tramontana, Manuela,Triolo, Antonio,Maggi, Carlo Alberto
-
experimental part
p. 65 - 78
(2010/11/16)
-
- DIAZEPANE COMPOUNDS WHICH MODULATE THE CB2 RECEPTOR
-
Compounds of formula (I) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.
- -
-
Page/Page column 32-33
(2009/05/30)
-
- BICYCLIC HETEROCYCLE DERIVATIVES AND USE THEREOF AS GPR119 MODULATORS
-
The present invention relates to Bicyclic Heterocycle Derivatives of formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of GPR1 19 in a patient.
- -
-
Page/Page column 164-165
(2009/12/27)
-
- MELANOCORTIN RECEPTOR AGONISTS
-
The present invention relates to a compound of the following formula 1, pharmaceutically acceptable salt and isomer thereof effective as agonist of melanocortin receptor, and an agonistic composition of melanocortin receptor comprising the same as active ingredient.
- -
-
Page/Page column 31
(2008/06/13)
-
- Process for Preparing Tetrahydropyran-4-Carboxylic Acid Compound
-
The present invention is to provide a process for preparing tetrahydropyran-4-carboxylic acid represented by the formula (1): which comprises hydrolyzing a 4-cyanotetrahydropyran-4-carboxylic acid compound represented by the formula (2): wherein R represents a hydrogen atom or a hydrocarbon group, in the presence of an acid; a process for preparing a tetrahydropyran-4-carboxylic acid ester which comprises reacting the tetrahydropyran-4-carboxylic acid represented by the above-mentioned formula (1) with an alcohol in the presence of an acid; and a process for preparing tetrahydropyran-4-carboxylic acid amide which comprises reacting the tetrahydropyran-4-carboxylic acid represented by the above-mentioned formula (1) with a halogenating agent to prepare tetrahydropyran-4-carboxylic acid halide, and then, reacting an amine compound to the resulting compound.
- -
-
Page/Page column 6
(2009/01/20)
-
- AMINOALCOHOL DERIVATIVES AND THEIR THERAPEUTIC USE
-
A compound of formula (1 ) Including pharmaceutically acceptable salts thereof, wherein: R1 is aryl or heteroaryl optionally substituted with R8; R2 is H or alkyl or CH2 (when forming part of a ring with R3
- -
-
Page/Page column 11-12
(2008/12/06)
-
- Imidazole compounds having an antiinflammatory effect
-
The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula I in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the i
- -
-
Page/Page column 34
(2008/06/13)
-
- 2-ALKYLBENZOXAZOLE CARBOXAMIDES AS 5HT3 MODULATORS
-
Compounds of formulae I and II: are disclosed as 5-HT3 inhibitors. Those compounds are useful in treating CINV, IBS-D and other diseases and conditions.
- -
-
Page/Page column 16-17
(2008/12/08)
-
- Discovery of a new series of potent and selective linear tachykinin NK 2 receptor antagonists
-
Starting from 1 (MEN 14268), a selective tachykinin NK2 receptor antagonist with an interesting in vitro pharmacological profile, a family of numerous antagonists was obtained through an optimization process focused on iterated structural modifications. The effects of the introduction of a wide variety of substituents on the lipophilic aromatic part of the molecule and the modulation of the structural constraint through the insertion of different achiral α,α-dialkylamino acids were investigated. In particular, aromatic and benzofused heteroaromatic moieties were introduced at the pseudo-N-terminal residue to replace the 2-benzothiophene moiety, and a systematic investigation of the best positioning of substituents onto the aromatic platform was reported for the benzothiophene core. Studies on the modulation of the length and the rigidity of the hydrophilic pseudo-C-terminal pendant are presented. Many heteroaliphatic groups are well tolerated by the receptor in this part of the ligand. The product 48f (MEN15596), bearing a methyl substituent on the benzothiophene and a tetrahydropyranylmethylpiperidine pendant, was finally selected for its good in vivo activity after intravenous, intraduodenal, and oral administration in guinea pigs.
- Fedi, Valentina,Altamura, Maria,Catalioto, Rose-Marie,Giannotti, Danilo,Giolitti, Alessandro,Giuliani, Sandro,Guidi, Antonio,Harmat, Nicholas J. S.,Lecci, Alessandro,Meini, Stefania,Nannicini, Rossano,Pasqui, Franco,Tramontana, Manuela,Triolo, Antonio,Maggi, Carlo Alberto
-
p. 4793 - 4807
(2008/03/12)
-
- SUBSTITUTED PYRAZOLE COMPOUNDS USEFUL AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
-
Disclosed are compounds active against soluble epoxide hydrolase (sEH), compositions thereof and methods of using and making same.
- -
-
Page/Page column 156-157
(2008/06/13)
-
- The "reverse-tethered" ruthenium (II) catalyst for asymmetric transfer hydrogenation: Further applications
-
The attachment of a tethering group from the basic nitrogen atom to the arene ligand of a ruthenium(II) catalyst greatly improves its ability to catalyze asymmetric transfer hydrogenation (ATH) reactions. In this paper, we describe further applications of this versatile system to an extended substrate range.
- Morris, David J.,Hayes, Aidan M.,Wills, Martin
-
p. 7035 - 7044
(2007/10/03)
-
- CHEMOKINE RECEPTOR BINDING COMPOUNDS
-
The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. Thesd compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
- -
-
Page/Page column 115
(2008/06/13)
-
- ESTER DERIVATIVES OF RHEIN AND THEIR THERAPEUTIC USE
-
Compounds that may have anti-inflammatory activity are of general formula (I); wherein X1, is H or COR1, and X2 is H or COR2 but X1, and X2are not both H; R1 and R2 are the same or different and are each C1-4 alkyl substituted with R3, or a four to seven-membered ring which can be optionally substituted with R8 and can contain one or more additional heteroatoms selected from O, S(O)n and NR9; is R3 is F, CF3, OR4, NR5R6 O, S(O)n R7 ; R4, R5 and R6 are the same or different and are each H or C1-4 alkyl optionally substituted with R3, or NR5R6 is a C4-6 heterocycloalkyl ring containing one or more heteroatoms selected from O, NR8 and S(O)n; each n is 0-2; R7 is C1-4 alkyl; R8 is as defined for R3 or C1-4 alkyl optionally substituted with R3 or halogen; and R9 is H or C1-4 alkyl; or a salt, solvate or hydrate thereof.
- -
-
Page/Page column 10
(2008/06/13)
-
- Benzimidazolone carboxylic acid derivatives
-
This invention relates to compounds of the formula (I): wherein R1, R2, R3, A and m are each as described herein or a pharmaceutically acceptable salt or solvate thereof, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5-HT4 receptor activity such as, but not limited to, gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders such as cardiac failure and heart arrhythmia, diabetes and apnea syndrome.
- -
-
Page/Page column 38
(2008/06/13)
-
- NOVEL PYRIDINE DERIVATIVES AS JNK SPECIFIC INHIBITORS
-
The present invention relates to new compounds of formula (I) wherein R is R3, R5, R6, COR5, COR6, CONHR3, CONHR5, CONHR6, CON(R6)2, COOR5, COOR6, SO2R5, SO2R6, OR3, OCOR3, COOR3, COR3, CONR3R4, NHCOR3, NR3R4, NHSO2R3, SO2R3, SO2NR3R4, SR3, CN, halogeno or NO2; R1 is aryl or heteroaryl each of which is optionally substituted with one or more of fluoro or chloro; R2 is R5, R6, COR5, COR6, CONHR5, CONHR6, CON(R6)2, COOR5, or COOR6; a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy.
- -
-
-
- ARYLPHENYLAMINO-, ARYLPHENYLAMIDE-, AND ARYLPHENYLETHER-SULFIDE DERIVATIVES
-
The present invention relates in part to compounds of formulas I and III: and pharmaceutically-acceptable salts and prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject.
- -
-
Page/Page column 140
(2010/02/14)
-
- Efficient synthesis of 3-aminocyclobut-2-en-1-ones: Squaramide surrogates as potent VLA-4 antagonists
-
(Matrix presented) A novel series of uniquely functionalized 3-aminocyclobut-2-en-1-ones has been prepared by facile condensation of a variety of cyclobuta-1,3-diones with a phenylalanine-derived primary amine. These systems subsequently lend themselves t
- Brand, Stephen,De Candole, Benjamin C.,Brown, Julien A.
-
p. 2343 - 2346
(2007/10/03)
-
- Syntheses and Binding Studies of New [(Aryl)(aryloxy)methyl]piperidine Derivatives and Related Compounds as Potential Antidepressant Drugs with High Affinity for Serotonin (5-HT) and Norepinephrine (NE) Transporters
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In a wide search program toward new, efficient, and fast-acting antidepressant drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl moiety linked directly or through a methylene chain to different substituted and unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or cyclopentane). These compounds have been evaluated for their affinities for serotonin (5-HT) transporter (SERT) and 5-HT1A and 5-HT2A receptors. Racemic mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher affinity values for SERT than fluoxetine and resulted in lack of affinity for 5-HT 1A and 5-HT2A receptors. Some of these racemic mixtures were resolved to their enantiomers and tested for binding to norepinephrine (NE) transporter (NET), dopamine (DA) transporter (DAT), and α2 receptor. Several of these enantiomers [(-)-15b, (-)-15j, (-)-15t, (+)-15u] displayed a dual binding profile with affinities for SERT and NET with K i i = 1.9 and 13.5 nM, respectively), and further pharmacological characterization is in progress for its evaluation as a antidepressant.
- Orjales, Aurelio,Mosquera, Ramón,Toledo, Antonio,Pumar, M. Carmen,García, Neftalí,Cortizo, Lourdes,Labeaga, Luis,Innerárity, Ana
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p. 5512 - 5532
(2007/10/03)
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- 112. Novel heterospirocyclic 3-amino-2H-azirines as synthons for heterocyclic α-amino acids)
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The heterospirocyclic N-methyl-N-phenyl-2H-azirin-3-amines (3-(N- methyl-N-phenylamino)-2H-azirines) 1a-d with a tetrahydro-2H-pyran, tetrahydro-2H-thiopyran, and a N-protected piperidine ring respectively, were synthesized from the corresponding heterocyclic 4-carboxamides 2 by consecutive treatment with lithium diisopropylamide (LDA), diphenyl phosphorochloridate (DPPCl), and sodium azide (Scheme 4). The reaction of these aminoazirines with thiobenzoic acid in CH2Cl2 at room temperature gave the thiocarbamoyl-substituted benzamides 13a-d in high yield. The azirines 1a-d were used as synthons for heterocyclic α-amino acids in the preparation of tripeptides of the type Z-Aib-Xaa-Aib-N(Ph)Me (18) by following the protocol of the 'azirine/ox-azolone method': treatment of Z- Aib with 1 to give the dipeptide amide 15, followed by selective hydrolysis to the corresponding acid 16 and coupling with the 2,2-dimethyl-2H-azirin-3- amine 17 gave 18, again in high yield (Scheme 5). With some selected examples of 18, the selective deprotection of the amino and the carboxy group, respectively, was demonstrated (Scheme 6). The solid-state conformations of the protected tripeptides 18a-d, as well as that of the corresponding carbocyclic analogue 18e, were determined by X-ray crystallography (Figs. 1- 3 and Tables 1-3). All five tripeprides adopt a β-turn conformation of type III or III. The solvent dependence of the chemical shifts of the NH resonances (Fig. 6) suggests that there is an intramolecular H-bond between H-N(4) and O(11) in all cases, which is an indication that a relatively rigid β-turn structure also persists in solution. Surprisingly, the tripeptide acid 20a shows no intramolecular H-bond in the crystalline state (Fig. 7); O(11) is involved in an intermolecular H-bond with the OH group of the carboxy function.
- Straessler, Christoph,Linden, Anthony,Heimgartner, Heinz
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p. 1528 - 1551
(2007/10/03)
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- Inhibition of human neutrophil elastase with peptidyl electrophilic ketones. 2. Orally active p(G)-Val-Pro-Val pentafluoroethyl ketones
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Valylprolylvalyl pentafluoroethyl ketones with different N-protecting groups were evaluated in vitro and in vivo as inhibitors of human neutrophil elastase (HNE). Several of these compounds were found to be orally active in HNE-induced rat and hamster lun
- Angelastro,Baugh,Bey,Burkhart,Chen,Durham,Hare,Huber,Janusz,Koehl,Marquart,Mehdi,Peet
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p. 4538 - 4553
(2007/10/02)
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