- Compound with degrading STAT3 enzyme and preparation method and pharmaceutical application thereof
-
The present invention relates to a compound represented by general formula (I) or a stereoisomer thereof. Use of deuterated, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or co-crystals, and intermediates and preparation methods, and in STAT3-related diseases such as tumors. B-L-K(I).
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-
- Cannabinoid receptor light-operated ligand and preparation method and application thereof
-
The invention relates to the technical field of biology, in particular to a novel cannabinoid receptor light-operated ligand and a preparation method and application thereof. Disclosed is the cannabinoid receptor light-operated ligand or the isomer prodrug, the solvate and the pharmaceutically acceptable salt of the cannabinoid receptor light-operated ligand, wherein the structural formula of thecannabinoid receptor light-operated ligand is A-linker-B; A is a transmembrane domain ligand structure, and B is a light-operated element; Linker is a subunit which is linear and has no activity on acannabinoid receptor light-operated ligand. According to the invention, the cannabinoid receptor ligand is integrated with azobenzene through a proper connector, so that the ligand configuration is changed under an illumination condition, and the activation or inhibition state of the cannabinoid receptor is regulated and controlled.
- -
-
Paragraph 0066; 0073-0078
(2021/01/24)
-
- Thiamine hydrochloride as a recyclable organocatalyst for the efficient and chemoselective N-tert-butyloxycarbonylation of amines
-
Thiamin hydrochloride promoted highly efficient and ecofriendly approach has been described for the chemoselective N-tert-butyloxycarbonylation of amines under solvent-free conditions at ambient temperature. The demonstrated approach has been applicable for the N-Boc protection of variety of aliphatic, aryl, heteroaryl amines. The chemoselective protection of amino group occurs in chiral amines and amino alcohol without racemization in high yield. Thiamin hydrochloride is stable, economical, easy to handle and environmentally friendly.
- Ingale, Ajit P.,Garad, Dnyaneshwar N.,Ukale, Dattatraya,Thorat, Nitin M.,Shinde, Sandeep V.
-
supporting information
p. 3791 - 3804
(2021/11/04)
-
- Rational Remodeling of Atypical Scaffolds for the Design of Photoswitchable Cannabinoid Receptor Tools
-
Azobenzene-embedded photoswitchable ligands are the widely used chemical tools in photopharmacological studies. Current approaches to azobenzene introduction rely mainly on the isosteric replacement of typical azologable groups. However, atypical scaffolds may offer more opportunities for photoswitch remodeling, which are chemically in an overwhelming majority. Herein, we investigate the rational remodeling of atypical scaffolds for azobenzene introduction, as exemplified in the development of photoswitchable ligands for the cannabinoid receptor 2 (CB2). Based on the analysis of residue-type clusters surrounding the binding pocket, we conclude that among the three representative atypical arms of the CB2 antagonist, AM10257, the adamantyl arm is the most appropriate for azobenzene remodeling. The optimizing spacer length and attachment position revealed AzoLig 9 with excellent thermal bistability, decent photopharmacological switchability between its two configurations, and high subtype selectivity. This structure-guided approach gave new impetus in the extension of new chemical spaces for tool customization for increasingly diversified photo-pharmacological studies and beyond.
- Hu, Tao,Hua, Tian,Li, Fei,Liu, Zhi-Jie,Makriyannis, Alexandros,Stevens, Raymond C.,Tao, Houchao,Tian, Cuiping,Xie, Linshan,Xu, Yueming,Xue, Dongxiang,Zhao, Fei,Zhao, Simeng,Zhao, Suwen,Zheng, Guoxun,Zhong, Guisheng,Zhou, Fang
-
p. 13752 - 13765
(2021/09/20)
-
- METHODS AND COMPOSITIONS FOR TARGETED PROTEIN DEGRADATION
-
Provided herein are methods and compositions for targeted protein degradation. In one aspect, a protein degradation chimera is provided, comprising: a first moiety that is capable of binding to a chaperone complex component; a second moiety that is capabl
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-
-
- PESTICIDAL COMPOSITIONS AND METHODS
-
This disclosure relates to the field of molecules having pesticidal utility against pests in phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses molecules having the structure of Formula A.
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Page/Page column 93
(2020/08/22)
-
- EP4 INHIBITORS AND SYNTHESIS THEREOF
-
The present invention provides N-((4-(2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenethyl)carbamoyl)-4-methylbenzenesulfonamide compositions, and the use thereof for treating a proliferative disorder.
- -
-
Paragraph 00526
(2020/02/06)
-
- Rapid and Selective Cleavage of Amide Groups at Neutral pH: Applications from Hyaluronic Acid to Small Molecules
-
During our investigation to find suitable conditions to prepare very high molecular weight partially de-acetylated hyaluronic acid (HA), we discovered a powerful new method to cleave amide bonds using hydroxylamine salts at neutral pH with remarkable sele
- Jing, Jing,Bankefors, Johan,Bonneaud, Céline,Sawen, Elin,Gerfaud, Thibaud,Westin, Jonatan,El-Bazbouz, Ghizlane,Kandelin, Lina,Rousseau, Antoine,Olsson, Johan,Karlsson, Anders,Nord, Lars,Bouix-Peter, Claire,Helander Kenne, Anne,Boiteau, Jean-Guy,Tomas, Loic,Hennequin, Laurent,Harris, Craig S.
-
supporting information
p. 2995 - 3000
(2018/06/27)
-
- Solid-Phase Enrichment and Analysis of Azide-Labeled Natural Products: Fishing Downstream of Biochemical Pathways
-
Many methods have been devised over the decades to trace precursors of specific molecules in cellular environments as, for example, in biosynthesis studies. The advent of click chemistry has facilitated the powerful combination of tracing and at the same time sieving the highly complex metabolome for compounds derived from simple or complex starting materials, especially when the click reaction takes place on a solid support. While the principle of solid-phase click reactions has already been successfully applied for selective protein and peptide enrichment, the successful enrichment of much smaller primary and secondary metabolites, showing great structural diversity and undergoing many different biosynthetic steps, has seen only little development. For bacterial secondary metabolism, a far broader tolerance for "clickable" precursors was observed than in ribosomal proteinogenesis, thus making this method a surprisingly valuable tool for the tracking and discovery of compounds within the cellular biochemical network. The implementation of this method has led to the identification of several new compounds from the bacterial genera Photorhabdus and Xenorhabdus, clearly proving its power.
- Pérez, Alexander J.,Wesche, Frank,Adihou, Hélène,Bode, Helge B.
-
supporting information
p. 639 - 645
(2016/01/12)
-
- Tailored near-infrared contrast agents for image guided surgery
-
The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for co
- Njiojob, Costyl N.,Owens, Eric A.,Narayana, Lakshminarayana,Hyun, Hoon,Choi, Hak Soo,Henary, Maged
-
p. 2845 - 2854
(2015/04/14)
-
- INHIBITORS OF METALLO-BETA-LACTAMASE (MBL) COMPRISING A ZINC CHELATING MOIETY
-
The invention provides compounds according to formula I: A - L - B wherein A represents a lipophilic chelating moiety which is selective for Zn2+ ions; L is a covalent bond or a linker; and B is a vector which is either a moiety capable of interacting with one or more biological structures found in a bacterium (preferably in a bacterial cell wall), for example a penicillin-binding protein such as a metallo-β- lactamase or DD-transferase, or a moiety capable of enhancing transport of the compound across a bacterial cell membrane. Such compounds find use in a method of treating and/or preventing a bacterial infection in a human or non-human mammal. In such a method, the compound of formula I may be administered in combination with (either simultaneously, separately, or sequentially) a β-lactam antibiotic.
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-
Page/Page column 29
(2015/04/22)
-
- Microwave-assisted protection of primary amines as 2,5-dimethylpyrroles and their orthogonal deprotection
-
Primary amines can be readily doubly protected as N-substituted 2,5-dimethylpyrroles. Although this protecting group is stable toward strong bases and nucleophiles, long reaction times are required for both the protection and deprotection steps, generally resulting in low deprotection yields. By employing microwave irradiation, protection and deprotection reaction times are dramatically reduced. Furthermore, deprotection with dilute hydrochloric acid in ethanol increases reaction yields. Diverse deprotection conditions have been developed in conjunction with microwave irradiation, so that protection as an N-substituted 2,5-dimethylpyrrole can be orthogonal to other standard amine protecting groups, such as tert-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), and 9-fluorenylmethyloxycarbonyl (Fmoc).
- Walia, Amit,Kang, Soosung,Silverman, Richard B
-
p. 10931 - 10937
(2013/11/19)
-
- Optical control of TRPV1 channels
-
Controlling pain with light: TRPV1 channels mediate the response to noxious heat and can be activated by capsaicin, the major ingredient of chili pepper. Novel azobenzene photoswitches can be used for the optical control of TRPV1. One of these compounds antagonizes capsaicin in a light-dependent fashion, demonstrating that a photoswitchable antagonist and an agonist can be applied in concert to modulate ion channel activity. Copyright
- Stein, Marco,Breit, Andreas,Fehrentz, Timm,Gudermann, Thomas,Trauner, Dirk
-
supporting information
p. 9845 - 9848
(2013/09/23)
-
- Indole-2-carboxamides as allosteric modulators of the cannabinoid CB 1 receptor
-
We synthesized new N-phenylethyl-1H-indole-2-carboxamides as the first SAR study of allosteric modulators of the CB1 receptor. The presence of the carboxamide functionality was required in order to obtain a stimulatory effect. The maximum stimulatory activity on CB1 was exerted by carboxamides 13 (EC50 = 50 nM) and 21 (EC50 = 90 nM) bearing a dimethylamino or piperidinyl group, respectively, at position 4 of the phenethyl moiety and a chlorine atom at position 5 of the indole.
- Piscitelli, Francesco,Ligresti, Alessia,La Regina, Giuseppe,Coluccia, Antonio,Morera, Ludovica,Allarà, Marco,Novellino, Ettore,Di Marzo, Vincenzo,Silvestri, Romano
-
p. 5627 - 5631
(2012/08/28)
-
- A multivalent approach to the discovery of long-acting β2- adrenoceptor agonists for the treatment of asthma and COPD
-
A multivalent approach was applied to the design of long-acting inhaled β2-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting β2-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C2-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection.
- Jacobsen, John R.,Choi, Seok Ki,Combs, Jesse,Fournier, Eric J.L.,Klein, Uwe,Pfeiffer, Juergen W.,Thomas, G. Roger,Yu, Cecile,Moran, Edmund J.
-
scheme or table
p. 1213 - 1218
(2012/03/11)
-
- INHIBITION OF BACTERIAL BIOFILMS WITH ARYL CARBAMATES
-
Disclosure is provided for carbamate compounds that prevent, remove and/or inhibit the formation of biofilms, compositions including these compounds, devices including these compounds, and methods of using the same.
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Page/Page column 33-34
(2012/02/01)
-
- Synthesis and pharmacological evaluation of dual acting antioxidant a 2A adenosine receptor agonists
-
A series of adenosine-5′-N-alkylcarboxamides and N 6-(2,2-diphenylethyl)adenosine-5′-N-alkylcarboxamides bearing antioxidant moieties in the 2-position were synthesized from the versatile intermediate, O6-(benzotriazol-1-yl)-2-fluoro
- Hausler, Nicholas E.,Devine, Shane M.,McRobb, Fiona M.,Warfe, Lyndon,Pouton, Colin W.,Haynes, John M.,Bottle, Steven E.,White, Paul J.,Scammells, Peter J.
-
experimental part
p. 3521 - 3534
(2012/06/04)
-
- BI-FUNCTIONAL QUINOLINE ANALOGS
-
Provided are compounds of Formula I: wherein X is: R1 and R2 together with the phenyl to which they are bound may form a bicyclic, fused heterocyclic ring, and all other variables are as defined herein, as well as their use in treating pulmonary inflammation or bronchoconstriction and compositions comprising and processes for preparing the same.
- -
-
Paragraph 0328
(2013/03/26)
-
- NEW BRADYKININ B1 ANTAGONISTS
-
The invention relates to compounds of formula (I) where in R1, R1a, R1b, R2, R3 and X, X1, X2, X3 have the meaning as cited in the description and the claims. Said compounds are useful as Bradykinin B1 antagonists. The invention also relates to pharmaceutical compositions, the preparation of such compounds as well as the production and use as medicament.
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Page/Page column 60
(2010/04/03)
-
- Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors
-
N-Oxalylglycine (NOG) derivatives were synthesized, and their inhibitory effect on histone lysine demethylase activity was evaluated. NOG and compound 1 inhibited histone lysine demethylases JMJD2A, 2C and 2D in enzyme assays, and their dimethyl ester prodrugs DMOG and 21 exerted histone lysine methylating activity in cellular assays.
- Hamada, Shohei,Kim, Tae-Dong,Suzuki, Takayoshi,Itoh, Yukihiro,Tsumoto, Hiroki,Nakagawa, Hidehiko,Janknecht, Ralf,Miyata, Naoki
-
scheme or table
p. 2852 - 2855
(2010/07/03)
-
- FLUORESCENT SUBSTRATES FOR MONOAMINE TRANSPORTERS AS OPTICAL FALSE NEUROTRANSMITTERS
-
The present invention relates to compounds of the general structure: wherein Y is O, X is O, bond α is absent and bond β is present, or Y is H, X is CH, bond α is present, and bond β is absent; atom Z is a carbon and bonds χ, δ and γ are present, or is a nitrogen and bonds χ, δ and γ are absent; R1 is -H, -OH, -O-R7, -N(H) -R8, -N (H) - (CH2) n-NH2, -N(R9) (R10), or a piperazine cation; R2 is either covalently bound to R9, or is -H, or is covalently bound to R3 so as to form a substituted or unsubstituted pyrrole or R2 is covalently bound to R9 or R8 or R7; or R1 and R2 are covalently joined to form an aromatic ring; R3 is either covalently bound to R2 so as to form a pyrrole, or is, inter alia, -H, -OH, alkyl, or when Z is nitrogen R3 is =O; R4 is, inter alia, -H, -OH, or -R11NH2; R5 is, inter alia, -H, -OH, or -R12NH2, and R6 is either is covalently bound to R10 or is -H, or R6 is covalently bound to R10 or R8 or R7. This invention also provides processes for making the compounds as well as methods for monitoring activity of monoamine transporters or treating monoamine transporter-associated diseases by employing the compounds.
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-
- Selective neuronal nitric oxide synthase inhibitors
-
Peptidomimetic compositions for selective inhibition of neuronal nitric oxide synthase.
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-
Page/Page column 31
(2009/01/24)
-
- Compounds for binding to ERalpha/beta and GPR30, methods of treating disease states and conditions mediated through these receptors and identification thereof
-
The current invention is in the field of molecular biology/pharmacology and provides compounds which modulate the effects of GPR30 as well as the classical estrogen receptors alpha and beta (ERα and ERβ). These compounds may function as agonists and/or an
- -
-
Page/Page column 16
(2008/12/06)
-
- New amide derivatives as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity
-
Melanin-concentrating hormone (MCH) is a recently discovered central nervous system (CNS) target for treating obesity. Two novel series of amide derivatives were synthesized and evaluated biologically as MCH-R1 (melanin-concentrating hormone receptor 1) antagonists. The results showed that diphenyl substituents on the amide lead to better activity than biphenyl substituents. ECV Editio Cantor Verlag.
- Cirauqui, Nuria,Ceras, Javier,Galiano, Silvia,Perez-Silanes, Silvia,Juanenea, Laura,Rivera, Gildardo,Aldana, Ignacio,Monge, Antonio
-
experimental part
p. 585 - 591
(2009/04/06)
-
- AMINOETHYLAROMATIC COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF THE DOPAMINE D3 RECEPTOR
-
The present invention relates to aromatic compounds of the formula (I) wherein Ar is phenyl or an aromatic 5-or 6-membered C-bound heteroaromatic radical, wherein Ar may carry 1 radical Ra and wherein Ar may also carry 1 or 2 radicals Rb; X is N or CH; E is CR6R7 or NR3;R1 is C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated Cl-C4--alkyl, fluorinated C3-C4-cycloalkyl, fluorinated C3-C 4-cycloalkylmethyl, fluorinated C3-C4--alkenyl, formyl or C1-C3-alkylcarbonyl; R1a is H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1--C4-alkyl, fluorinated C3-C4-cycloalkyl, fluorinated C 3-C4-cycloalkylmethyl, fluorinated C3--C 4-alkenyl, or R1a and R2 together are (CH 2)n with n being 2, 3 or 4, or R1a and R 2a together are (CH2)n with n being 2, 3 or 4; R2 and R2a are independently of each other H, C1-C4-alkyl or fluorinated C1-C 4-alkyl or R2a and R2 together are (CH 2)m with m being 1, 2, 3, 4 or 5; R3 is H or C1-C4-alkyl; R6, R7 independently of each other are selected from H, fluorine, C1-C4-alkyl and fluorinated C1-C4-alkyl or together form a moiety (CH2)p with p being 2, 3, 4 or 5; and the physiologically tolerated acid addition salts thereof. The invention also relates to the use of a compound of the formula (I) or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a dopamine D3 receptor ligand.
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Page/Page column 99
(2010/11/08)
-
- Pyrimidine compounds
-
This invention relates to a method for treating inflammatory diseases or immune diseases, developmental or degenerative diseases, or tissue injuries. The method includes administering to a subject in need thereof an effective amount of one or more compounds of formula (I). Each variable in this formula is defined in the specification.
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-
Page/Page column 119-121
(2008/06/13)
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- AMINO-SUBSTITUTED ETHYLAMINO Beta2 ADRENERGIC RECEPTOR AGONISTS
-
The invention provides novel beta2 adrenergic receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with beta2 adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.
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Page/Page column 40
(2008/06/13)
-
- 1H-IMIDAZO[4,5-C]QUINOLINE DERIVATIVES IN THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES
-
The invention relates to the use of imidazoquinolines and salts thereof in the treatment of protein kinase diseases and for the manufacture of pharmaceutical preparations for the treatment of said diseases, imidazoquinolines for use in the treatment of protein kinase dependent diseases, a method of treatment against said diseases, comprising administering the imidazoquinolines to a warm-blooded animal, especially a human, pharmaceutical preparations comprising an imidazoquinoline, especially for the treatment of a protein kinase dependent disease, novel imidazoquinolines, and a process for the preparation of the novel imidazoquinolines.
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Page/Page column 64
(2010/02/12)
-
- 2-(AMINO-SUBSTITUTED)-4-ARYL PYRAMIDINES AND RELATED COMPOUNDS USEFUL FOR TREATING INFLAMMATORY DISEASES
-
A heterocyclic inhibitor having the formula (I), with the variables defined herein, which is useful for treating inflammatory and other physiological disorders in which PKC-theta isoform plays a role.
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Page/Page column 131
(2008/06/13)
-
- Novel inhibitors of neuronal nitric oxide synthase with potent antioxidant properties.
-
A series of hybrid compounds possessing an nNOS pharmacophore linked to an antioxidant fragment has been synthesized. Among them, compound 8d, a propofol derivative, displayed the greatest dual potencies against nNOS (IC(50)=0.12 microM) and lipid peroxidation (IC(50)=0.4 microM) accompanied with e/nNOS selectivity (67.5). This shows that nNOS was able to accommodate very bulky groups such as di-tert-butyl or di-iso-propyl phenol in its active site.
- Auvin, Serge,Auguet, Michel,Navet, Edith,Harnett, Jeremiah J,Viossat, Isabelle,Schulz, Jocelyne,Bigg, Dennis,Chabrier, Pierre E
-
p. 209 - 212
(2007/10/03)
-
- Substituted alkylamine derivatives and methods of use
-
Selected amines are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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-
Page 49; 113
(2010/02/05)
-
- Substituted alkylamine derivatives and methods of use
-
Selected heterocyclic compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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-
-
- Aromatic reduced amide bond peptidomimetics as selective inhibitors of neuronal nitric oxide synthase
-
Nitric oxide synthase inhibitors could act as important therapies for disorders arising from overstimulation or overexpression of individual nitric oxide synthase (NOS) isoforms. But preservation of physiologically important nitric oxide functions require the use of isoform-selective inhibitors. Recently we reported reduced amide bond pseudodipeptide analogues as potent and selective neuronal nitric oxide synthase (nNOS) inhibitors (Hah, J.-M.; Roman, L. J.; Martasek, P.; Silverman, R. B. J. Med. Chem. 2001, 44, 2667-2670). To increase the lipophilicity a series of aromatic, reduced amide bond analogues (6-25) were designed and synthesized as potential selective nNOS inhibitors. The hypothesized large increase in isoform selectivity of nNOS over inducible NOS was not obtained in this series. However, the high potency with nNOS as well as high selectivity of nNOS over endothelial NOS was retained in some of these compounds (15, 17, 21), as well as good selectivity over inducible NOS. The most potent nNOS inhibitor among these compounds is N-(4S)-{4-amino-5-[2-(2-aminoethyl)-phenylamino]-pentyl}-N′- nitroguanidine (17) (Ki = 50 nM), which also shows the highest selectivity over eNOS (greater than 2100-fold) and 70-fold selectivity over iNOS. Further modification of compound 17 should lead to even more potent and selective nNOS inhibitors.
- Hah, Jung-Mi,Martásek, Pavel,Roman, Linda J.,Silverman, Richard B.
-
p. 1661 - 1669
(2007/10/03)
-
- Imidazole compounds as anti-inflammatory and analgesic agents
-
This invention provides a compound of the formula (I): wherein: R1 represents a hydrogen atom, an alkyl group, etc.; R2 represents a hydrogen atom, a halogen atom, etc.; R3 represents a hydrogen atom, an alkyl group, etc.;
- -
-
Page/Page column 37
(2010/02/03)
-
- Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor
-
Disclosed are novel compounds having the formula or a physiologically acceptable salt, amide, ester or prodrug thereof. The compounds can be used to modulate (antagonize, agonize) chemokine receptor function. Also disclosed is a method for treating a patient having an inflammatory disease and/or viral infection comprising administering an effective amount of a compound of Formula I. In particular embodiments, the invention is a method for treating a patient infected with HIV.
- -
-
-
- Substituted arylsulfides, arylsulfoxides and arylsulfones as beta-3 adrenergic receptor agonists
-
This invention provides compounds of Formula I having the structure wherein R1, R2, R3, R4, R5, R6, Y, Z, m, n, and are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type 11 diabetes.
- -
-
-
- Tetrahydroindazole derivatives as ligands for GABA-A α 5 receptors
-
4-oxo-tetrahydroindozole-3-carboxamide compounds according to Formula (I), or a pharmaceutically acceptable salt thereof, are GABA-A Alpha 5 ligands useful for enhancing cognition:
- -
-
-
- HETEROCYCLIC BETA-3 ADRENERGIC RECEPTOR AGONISTS
-
This invention provides compounds of Formula I having the structure U, V, W, X, and Y are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
- -
-
-
- Thiophene integrin inhibitors
-
The present invention comprises compounds that are effective inhibitors of integrins, particularly αvβ3 and αvβ5 integrins. Particularly, the compounds are of formula I and pharmaceutically acceptable salts thereof wherein X,Y1W, R1 to R5, A and B are defined according to the disclosure herein.
- -
-
-
- 4-Aminopiperidine ureas as potent selective agonists of the human β3-Adrenergic receptor
-
The preparation and structure-activity relationships (SARs) of potent agonists of the human β3-adrenergic receptor (AR) derived from a 4-aminopiperidine scaffold are described. Examples combine human β3-AR potency with selectivity over human β1-AR and/or human β2-AR agonism. Compound 29s was identified as a potent (EC50 = 1 nM) and selective (greater than 400-fold over β1- with no β2-AR agonism) full β3-AR agonist with in vivo activity in a transgenic mouse model of thermogenesis.
- Ashwell, Mark A,Solvibile Jr., William R,Han, Stella,Largis, Elwood,Mulvey, Ruth,Tillet, Jeffrey
-
p. 3123 - 3127
(2007/10/03)
-
- A novel series of 2-carboxytetrahydroquinolines provides new insights into the eastern region of glycine site NMDA antagonists
-
A series of potent 4-substituted tetrahydroquinolines has been synthesized and biologically tested in order to refine the eastern region of the pharmacophore model for glycine site NMDA antagonists concerning the assessment of lipophilicity, flexibility, and hydrogen bonding. Displacement studies on rat cortical membranes using [3H]-5,7-dichlorokynurenic acid as a radioligand indicated that binding affinities are markedly enhanced when additional hydrogen-accepting groups are introduced into the eastern region of the 2-carboxytetrahydroquinolines. Among the most potent ligands were some urea, sulfonylurea, and crown ether compounds as interesting leads for new diagnostics, especially for the evaluation of PET tracers, which allow biodistribution studies and NMDA receptor studies in the living organism.
- Dannhardt, Gerd,Gruchalla, Markus V.,Kohl, Beate K.,Parsons
-
p. 267 - 274
(2007/10/03)
-
- Substituted analogues of GV150526 as potent glycine binding site antagonists in animal models of cerebral ischemia
-
A series of analogues of the indole-2-carboxylate GV150526, currently in clinical trials as a potential neuroprotective agent for the control of the cerebral damage after stroke onset, was designed based on previous studies dealing with the electronic features of the north-east region of the glycine binding site associated with the NMDA receptor. In particular, the substitution of the para position of the terminal phenyl ring of GV150526 with suitable hydrophilic groups resulted in the identification of a new class of glycine antagonists. These compounds exhibited nanomolar in vitro affinity to the glycine binding site, high receptor selectivity, and outstanding in vivo potency. In particular, 3-[(E)-2-[(4- ureidomethylphenyl)aminocarbonyl]ethenyl]-4,6-dichloroindole-2-carboxylic acid was found to be highly effective in the middle cerebral artery occlusion (MCAo) model in the rat, an animal model of focal ischemia, when given both prior to and after the occlusion of the middle cerebral artery. Notably, a significant neuroprotective effect was seen in this model postischamia, when the administration of this compound was delayed up to 6 h from the occlusion of the middle cerebral artery, further confirming the wide therapeutic window seen for GV150526A.
- Di Fabio, Romano,Conti, Nadia,De Magistris, Elisabetta,Feriani, Aldo,Provera, Stefano,Sabbatini, Fabio Maria,Reggiani, Angelo,Rovatti, Luca,Barnaby, Robert J.
-
p. 3486 - 3493
(2007/10/03)
-
- Heterocyclic compouds
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A compound of the general formula wherein: n is 0 or 1; M1 is an amino group; Q is an aromatic heterocyclic group containing a basic nitrogen atom; M2 is an imino group; L is a template group; and A is an acidic group, or an ester or amide derivative thereof, or a sulphonamide group; and pharmaceutically acceptable salts and pro-drugs thereof, for use in the treatment of a disease in which platelet aggregation mediated by the binding of adhesion molecules to GPIIb-IIIa is involved. Novel compounds are also disclosed.
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- Substituted phenyl sulfonamides as selective β 3 agonists for the treatment of diabetes and obesity
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Substituted phenylsulfonamides are selective β 3 adrenergic receptor agonists with very little β 1 and β 2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted alkyl epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.
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- Synthesis and Evaluation of Novel Spermidine Derivatives as Targeted Cancer Chemotherapeutic Agents
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The utility of the spermidine moiety as the homing device for the selective delivery of chemotherapeutic and diagnostic agents into cancer cells was explored.Two spermidine analogs containing a cytotoxic agent were synthesized, N-3,4-bis(benzyloxy)phenet
- Stark, Peter A.,Thrall, Brian D.,Meadows, Gary G.,Abdel-Monem, Mahmoud M.
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p. 4264 - 4269
(2007/10/02)
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