- Rational design of a fluopyram hapten and preparation of bioconjugates and antibodies for immunoanalysis
-
A fluopyram hapten was designed in which insignificant electronic and structural modifications were foreseen and all potentially interacting chemical moieties were maintained. This hapten was prepared by total synthesis and three immunologically active bi
- Ceballos-Alcantarilla,Agulló,Abad-Fuentes,Abad-Somovilla,Mercader
-
p. 51337 - 51341
(2015/06/25)
-
- Heterocyclic compounds
-
The invention relates to compounds of Formula I: wherein Ar1, Ar2, Ar3, L1, L2, Y, Z and v are defined in the specification, and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of Formula I or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of Formula I or a pharmaceutically acceptable derivative thereof.
- -
-
Page/Page column 87-88
(2015/11/09)
-
- Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 4. Exploration of a novel binding pocket
-
Structure-activity relationship investigations conducted at the 5-position of the N-pyridine ring of a series of N-arylsulfonyl-N′-2-pyridinyl- piperazines led to the identification of a novel bis-pyridinyl piperazine sulfonamide (51) that was a potent disruptor of the glucokinase-glucokinase regulatory protein (GK-GKRP) interaction. Analysis of the X-ray cocrystal of compound 51 bound to hGKRP revealed that the 3-pyridine ring moiety occupied a previously unexplored binding pocket within the protein. Key features of this new binding mode included forming favorable contacts with the top face of the Ala27-Val28-Pro29 ("shelf region") as well as an edge-to-face interaction with the Tyr24 side chain. Compound 51 was potent in both biochemical and cellular assays (IC50 = 0.005 μM and EC 50 = 0.205 μM, respectively) and exhibited acceptable pharmacokinetic properties for in vivo evaluation. When administered to db/db mice (100 mg/kg, po), compound 51 demonstrated a robust pharmacodynamic effect and significantly reduced blood glucose levels up to 6 h postdose.
- Hong, Fang-Tsao,Norman, Mark H.,Ashton, Kate S.,Bartberger, Michael D.,Chen, Jie,Chmait, Samer,Cupples, Rod,Fotsch, Christopher,Jordan, Steven R.,Lloyd, David J.,Sivits, Glenn,Tadesse, Seifu,Hale, Clarence,St. Jean, David J.
-
p. 5949 - 5964
(2014/08/18)
-
- N-(HETEROARYL)-SULFONAMIDE DERIVATIVES USEFUL AS S100-INHIBITORS
-
A compound of formula (I), or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the compound. The compound is an inhibitor of interactions between S100A9 and interaction partners such as RAGE, TLR4 and EMMPRIN and as such is useful in the treatment of disorders such as cancer, autoimmune disorders, inflammatory disorders and neurodegenerative disorders.
- -
-
Page/Page column 100
(2014/12/12)
-
- 4-Azolylphenyl isoxazoline insecticides acting at the GABA gated chloride channel
-
Isoxazoline insecticides have been shown to be potent blockers of insect GABA receptors with excellent activity on a broad pest range, including Lepidoptera and Hemiptera. Herein we report on the synthesis, biological activity and mode-of-action for a class of 4-heterocyclic aryl isoxazoline insecticides.
- Lahm, George P.,Cordova, Daniel,Barry, James D.,Pahutski, Thomas F.,Smith, Ben K.,Long, Jeffrey K.,Benner, Eric A.,Holyoke, Caleb W.,Joraski, Kathleen,Xu, Ming,Schroeder, Mark E.,Wagerle, Ty,Mahaffey, Michael J.,Smith, Rejane M.,Tong, My-Hahn
-
p. 3001 - 3006
(2013/06/26)
-
- Substituted-nicotinyl thiourea derivatives bearing pyrimidine moiety: Synthesis and biological evaluation
-
A series of substituted-nicotinyl thiourea derivatives containing pyrimidine ring were synthesized in good to excellent yield using PEG-400 as solid-liquid phase transfer catalyst under ultrasonic irradiation. The structures of all newly synthesized compounds were elucidated and confirmed by IR, 1H NMR and elemental analysis. The preliminary biological tests show that some of the target compounds present good inhibitory activities against the root and stalk of dicotyledon plants and are safe for monocotyledon plants.
- Ke, Shaoyong,Cao, Xiufang
-
experimental part
p. 627 - 633
(2012/04/23)
-
- MONOCYCLIC COMPOUNDS AND THEIR USE AS TRPV1 LIGANDS
-
The invention relates to compounds of formula I and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof.
- -
-
Page/Page column 95
(2010/06/11)
-
- HETEROCYCLIC TRPV1 RECEPTOR LIGANDS
-
The invention relates to compounds of formulae I(a)-I(d): and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formulae I(a)-I(d) or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formulae I(a)-I(d) or a pharmaceutically acceptable derivative thereof.
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-
Page/Page column 169-170
(2010/06/16)
-
- BICYCLOHETEROARYL COMPOUNDS AND THEIR USE AS TRPV1 LIGANDS
-
The invention relates to compounds of formula I and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof.
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-
Page/Page column 123
(2010/06/14)
-
- HETEROARYLOXY QUINAZOLINE DERIVATIVE
-
Disclosed are compounds of the following formula and their pharmaceutically-acceptable salts, which have an effect of glucokinase activation and are useful in the field of medicines for treatment for diabetes, obesity, etc. (wherein ring A represents a pyrazolyl group optionally having a lower alkyl group, etc.; ring B represents a heteroaryl group; R represents a lower alkyl group, etc.; R1 represents a group of a formula: (wherein R11 and R12 each independently represent a hydrogen atom, etc.; m indicates an integer of from 2 to 6), etc.; R2 represents a lower alkyl group, etc.; r indicates an integer of from 0 to 3; k indicates an integer of from 0 to 4).
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-
Page/Page column 72
(2010/09/05)
-
- Organic compounds
-
The present invention relates to novel benzimidazole derivatives, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them, wherein the compounds have the formula (I): in which the substitutents are as defined in claim 1 and salts, solvates, hydrates and N-oxides thereof.
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Page/Page column 22
(2009/05/29)
-
- TETRAHYDROCYCLOPENTA[B]INDOL-3-YL CARBOXYLIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
-
The present invention relates to certain (1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl carboxylic acid derivatives of Formula (Ia) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1 associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, microbial infections or diseases and viral infections or diseases.
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Page/Page column 94-95
(2009/07/18)
-
- NICOTINIC ACID DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR-5
-
The present invention relates to novel benzimidazole derivatives, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them, wherein the compounds have the Formula (I): in which the substitutents are as defined in claim 1 and and salts, solvates, hydrates and N- oxides thereof.
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-
Page/Page column 58
(2008/12/08)
-
- TRPV1 ANTAGONISTS AND USES THEREOF
-
The invention relates to compounds of formula (I) and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof.
- -
-
Page/Page column 305
(2008/12/08)
-
- THERAPEUTIC AGENTS USEFUL FOR TREATING PAIN
-
A compound of Formula: (I) or a pharmaceutically acceptable derivative thereof, where Ar1, Ar2, X, R3, and m are as disclosed herein. Compounds of Formulae (I)-(V) and pharmaceutically acceptable derivatives thereof; compositions comprising an effective amount of a compound of Formulae (I)-(V) or a pharmaceutically acceptable derivative thereof; and methods for treating or preventing pain, UI, an ulcer, IBD, or IBS in an animal comprising administering to an animal in need thereof an effective amount of a compound of Formulae (I)-(V) or a pharmaceutically acceptable derivative thereof are disclosed herein.
- -
-
Page/Page column 72; 73
(2008/12/08)
-
- AMINOTHIAZOLE DERIVATIVES AS AGONISTS OF THE THROMBOPOIETIN RECEPTOR
-
A compound of the formula (I) wherein R1, R2, R3, X, Y, and d are defined as above. The presently disclosed compounds are TPO agonists useful as promoters of thrombopoiesis and megakaryocytopoiesis.
- -
-
Page/Page column 45
(2010/11/26)
-
- NICOTINIC ACID DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
-
The present invention relates to novel nicotinic acid derivatives, of formula (I), wherein the substituents are defined in the specification, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them.
- -
-
Page/Page column 31
(2008/06/13)
-
- Antimicrobial lexitropsins containing amide, amidine, and alkene linking groups
-
The synthesis and properties of 80 short minor groove binders related to distamycin and the thiazotropsins are described. The design of the compounds was principally predicated upon increased affinity arising from hydrophobic interactions between minor groove binders and DNA. The introduction of hydrophobic aromatic head groups, including quinolyl and benzoyl derivatives, and of alkenes as linkers led to several strongly active antibacterial compounds with MIC for Staphylococcus aureus, both methicillin-sensitive and -resistant strains, in the range of 0.1-5 μg mL-1, which is comparable to many established antibacterial agents. Antifungal activity was also found in the range of 20-50 μg mL-1 MIC against Aspergillus niger and Candida albicans, again comparable with established antifungal drugs. A quinoline derivative was found to protect mice against S. aureus infection for a period of up to six days after a single intraperitoneal dose of 40 mg kg-1.
- Anthony, Nahoum G.,Breen, David,Clarke, Joanna,Donoghue, Gavin,Drummond, Allan J.,Ellis, Elizabeth M.,Gemmell, Curtis G.,Helesbeux, Jean-Jacques,Hunter, Iain S.,Khalaf, Abedawn I.,Mackay, Simon P.,Parkinson, John A.,Suckling, Colin J.,Waigh, Roger D.
-
p. 6116 - 6125
(2008/09/16)
-
- AMINOTHIAZOLE DERIVATIVES AS AGONISTS OF THE THROMBOPOIETIN RECEPTOR
-
A compound of the formula (I) wherein R1, R2, R3, X, and d are defined as above. The presently disclosed compounds are TPO agonists useful as promoters of thrombopoiesis and megakaryocytopoiesis.
- -
-
Page/Page column 52
(2010/11/25)
-
- A novel class of potent influenza virus inhibitors: Polysubstituted acylthiourea and its fused heterocycle derivatives
-
A series of polysubstituted and fused heterocycle derivatives of acylthiourea was prepared and the biological activity against influenza virus was evaluated. Of the analogues that demonstrated IC50s 0.1 μM, acylthiourea derivatives 16 and 50 were further investigated as candidates with the most potential for future development. The SAR of these compounds are discussed and they represent a novel class of highly potent and selective inhibitors of influenza virus.
- Sun, Chuanwen,Huang, Hai,Feng, Meiqing,Shi, Xunlong,Zhang, Xiaodong,Zhou, Pei
-
p. 162 - 166
(2007/10/03)
-
- Efficient synthesis of novel NK1 receptor antagonists: Selective 1,4-addition of Grignard reagents to 6-chloronicotinic acid derivatives
-
A new efficient synthesis of two novel classes of NK1 receptor antagonists, among them befetupitant and netupitant, starting from 6-chloronicotinic acid is described. The introduction of the o-tolyl substituent at C(4) of the pyridine ring was achieved by a one-pot selective 1,4-Grignard addition/oxidation sequence to 6-chloronicotinic acid or a derivative of it. The scope of this addition/oxidation sequence was examined. It was also shown that the carboxylic function can be converted to a methyl amino group by a Hofmann rearrangement followed by reduction. Furthermore, a new high-yielding synthesis of 2-(3,5-bistrifluoromethylphenyl)-2-methyl propionic acid based on the carbonylation of the tertiary alcohol obtained by Grignard addition of 3,5-bis(trifluoromethyl)bromobenzene to acetone was established.
- Hoffmann-Emery, Fabienne,Hilpert, Hans,Scalone, Michelangelo,Waldmeier, Pius
-
p. 2000 - 2008
(2007/10/03)
-
- Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure-activity relationships of 2-piperazin-1-yl-1H- benzimidazoles
-
The vanilloid receptor-1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2- ylpiperazin-1-yl)-1H-benzo-[d]imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant (CFA).
- Ognyanov, Vassil I.,Balan, Chenera,Bannon, Anthony W.,Bo, Yunxin,Dominguez, Celia,Fotsch, Christopher,Gore, Vijay K.,Klionsky, Lana,Ma, Vu V.,Qian, Yi-Xin,Tamir, Rami,Wang, Xianghong,Xi, Ning,Xu, Shimin,Zhu, Dawn,Gavva, Narender R.,Treanor, James J. S.,Norman, Mark H.
-
p. 3719 - 3742
(2007/10/03)
-
- Synthesis and evaluation of a new series of substituted acyl(thio)urea and thiadiazolo [2,3-a] pyrimidine derivatives as potent inhibitors of influenza virus neuraminidase
-
A series of substituted acyl(thio)urea and 2H-1,2,4-thiadiazolo [2,3-a] pyrimidine derivatives were prepared and both of their cell culture and enzymatic activity toward influenza virus were tested. Their in vitro neuraminidase inhibitory activities were in good agreement with the corresponding activities in cultured cells and they were evaluated as potent neuraminidase inhibitors. Of the analogues that demonstrated IC50s 0.1 μM, 16 and 60 were further investigated as candidates with the most potential for future development. The molecular docking work of the representative compound was described to provide more insight into their mechanism of action and further rationalize the observations of this new series herein, which represents a novel class of highly potent and selective inhibitors of influenza virus.
- Sun, Chuanwen,Zhang, Xiaodong,Huang, Hai,Zhou, Pei
-
p. 8574 - 8581
(2008/02/07)
-
- NOVEL HETEROCYCLIC SUBSTITUTED PYRIDINE OR PHENYL COMPOUNDS WITH CXCR3 ANTAGONIST ACTIVITY
-
The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts, solvates or esters of said compound, or of said prodrug, said compound having the general structure shown in Formula 1 or a pharmaceutically acceptable salt, solvate or ester thereof. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non-limiting example(s) include, psoriasis), autoimmune diseases (non-limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non-limiting example(s) include, allograft rejection, zenograft rejection), infectious diseases (e.g , tuberculoid leprosy), fixed drug eruptions, cutaneous delayed-type hypersensitivity responses, ophthalmic inflammation, type I diabetes, viral meningitis and tumors using a compound of Formula 1.
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-
Page/Page column 107-108
(2008/06/13)
-
- PYRAZOLE COMPOUNDS AS PROSTAGLANDIN RECEPTORS LIGANDS
-
Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein Z, R1 ,R2a, R2b, R10, R11 and Rx are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.
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-
Page/Page column 76-77
(2008/06/13)
-
- 2-PHENYL SUBSTITUTED IMIDAZOL [4 , 5B] PYRIDINE/ PYRAZINE AND PURINE DERIVATIVES AS GLUCOKINASE MODULATORS
-
Compounds of Formula (I), wherein R1- R10, A and X1 to X3 are as described in the specification, and their salts and pro-drugs, are activators of glucokinase (GLK) and are thereby useful in the treatment of, for example, type 2 diabetes. Processes for preparing compounds of formula (I) are also described.
- -
-
Page/Page column 116
(2010/11/25)
-
- Ultrasonic irradiated synthesis and herbicidal activities of 5,7-disubstituted-2-(substituted pyridine-3-formylimino)-2H-1,2,4-thiadiazolo[2, 3-a]pyrimidine derivatives
-
Eight new substituted-pyridine-3-formylimino-2H-1,2,4-thiadiazolo[2,3-a] derivatives containing substituted pyrimidine ring were synthesized in good yield under ultrasonic irradiation (USI). The structures of all newly synthesized compounds were elucidated and confirmed by IR, 1H NMR and elemental analysis. The target compounds have been screened for activity against a number of monocotyledones and dicotyledones. The preliminary herbicidal tests show that some of the target compounds have better inhibitory activities against weeds.
- Xue, Sijia,Ke, Shaoyong,Duan, Liping,Wang, Xiuhua,Guo, Yanling
-
-
- (3,4-DISUBSTITUTED)PROPANOIC CARBOXYLATES AS S1P (EDG) RECEPTOR AGONISTS
-
The present invention encompasses compounds of Formula A: A as well as the pharmaceutically acceptable salts thereof. The compounds are S1P1/Edg1 receptor agonists and thus have immunosuppressive, anti-inflammatory and hemostatic activities by modulating leukocyte trafficking, sequestering lymphocytes in secondary lymphoid tissues, and enhancing vascular integrity. The invention is also directed to pharmaceutical compositions containing such compounds and methods of treatment or prevention.
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Page/Page column 67-68
(2008/06/13)
-
- BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS VANILLOID RECEPTOR LIGANDS
-
Compounds of formula (I) are useful in the treatment of vanilloid-receptor-meditated diseases, such as inflammatory or neuropathic pain and diseases involving sensory nerve function such as asthma, rheumatoid arthritis, osteoarthritis, inflammatory bowel disorders, urinary incontinence, migraine and psoriasis.
- -
-
-
- 2-(3-Amino-2-hydroxy-propoxy)-mono-and diazines
-
Heterocyclic compounds of the formula STR1 wherein Het denotes optionally substituted pyridazinyl, pyrimidinyl, pyrazinyl or substituted pyridyl, R1 is hydrogen or methyl and R2 is lower alklyl, optionally substituted phenyl-lower alkyl, carboxy-lower alkyl or functionally modified carboxy-lower alkyl, their condensation products with aldehydes, ketones or carbonic acid and their N-oxides, which are valuable (cardioselective) β-receptor blocking agents, and/or (cardioselective) β-receptor-stimulants.
- -
-
-
- 2-(3-AMINO-2-HYDROXY-PROPOXY)-PYRAZINES
-
Heterocyclic compounds of the formula STR1 wherein Het denotes optionally substituted pyridazinyl, pyrimidinyl, pyrazinyl or substituted pyridyl, R 1 is hydrogen or methyl and R 2 is lower alkyl, optionally substituted phenyl-lower alkyl, carboxy-lower alkyl or functionally modified carboxy-lower alkyl, their condensation products with aldehydes, ketones or carbonic acid and their N-oxides, which are valuable (cardioselective) β-rezeptor blocking agents, and/or (cardioselective) β-rezeptor-stimulants.
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-
-