- FLUOROINDOLE DERIVATIVES AS MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
-
The present invention relates to compound of formula (I), or stereoisomers and pharmaceutically acceptable salts as muscarinic M1 receptor positive allosteric modulators. This invention also relates to methods of making such compounds and pharmaceutical compositions comprising such compounds. The compounds of this invention are useful in the treatment of various disorders that are related to muscarinic M1 receptor.(Formula I) (I)
- -
-
Page/Page column 24; 25
(2017/03/28)
-
- INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
-
The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
- -
-
Paragraph 578; 579
(2016/10/11)
-
- Synthesis, biological evaluation and molecular docking studies of novel 2-(1,3,4-oxadiazol-2-ylthio)-1-phenylethanone derivatives
-
In present study, a series of new 2-(1,3,4-oxadiazol-2-ylthio)-1- phenylethanone derivatives (6a-6x) as potential focal adhesion kinase (FAK) inhibitors were synthesized. The bioassay assays demonstrated that compound 6i showed the most potent activity, which inhibited the growth of MCF-7 and A431 cell lines with IC50 values of 140 ± 10 nM and 10 ± 1 nM, respectively. Compound 6i also exhibited significant FAK inhibitory activity (IC50 = 20 ± 1 nM). Docking simulation was performed to position compound 6i into the active site of FAK to determine the probable binding model.
- Zhang, Li-Rong,Liu, Zhi-Jun,Zhang, Hui,Sun, Jian,Luo, Yin,Zhao, Ting-Ting,Gong, Hai-Bin,Zhu, Hai-Liang
-
scheme or table
p. 3615 - 3621
(2012/07/27)
-
- THIAZOLE AND OXAZOLE KINASE INHIBITORS
-
The present invention provides thiazole and oxazole compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
- -
-
Page/Page column 187
(2009/04/25)
-
- METHODS FOR TREATING CHRONIC PAIN USING 3-ARYL-3-HYDROXY-2-AMINO-PROPIONIC ACID AMIDES, 3-HETEROARYL-3-HYDROXY-2-AMINO-PROPIONIC ACID AMIDES AND RELATED COMPOUNDS
-
Disclosed herein are methods of treating a patient suffering from one or more types of chronic pain using compounds of Formulas 1 and 2 wherein the variables have the meaning disclosed in the specification
- -
-
Page/Page column 76
(2010/11/29)
-
- Pyridine Derivatives For Inhibiting Human Stearoyl-Coa-Desaturase
-
Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I) where x, y, G, J, K, L, M, W, V, R2, R3, R4, R5, R5a,
- -
-
Page/Page column 14
(2008/12/06)
-
- Pyrazolo[1,5-A]pyrimidine derivatives and methods of use thereof
-
The present invention relates to pyrazolo[1,5-a]pyrimidine derivatives, compositions comprising an effective amount of a pyrazolo[1,5-a]pyrimidine derivative and methods for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of a pyrazolo[1,5-a]pyrimidine derivative.
- -
-
Page/Page column 38
(2010/11/28)
-
- SELECTIVE INHIBITORS AGAINST Cdk4 AND Cdk6 HAVING AMINOTHIAZOLE SKELETON
-
The present invention relates to a compound represented by Formula [I]: wherein X is O, S, NH or CH 2 ; Y 1 , Y 2 , Y 3 , Y 4 and Y 5 , which may be identical or different, are each CH or N; however, at least one of Y 1 , Y 2 , Y 3 , Y 4 and Y 5 is N; Z 1 and Z 2 , which may be identical or different, are each CH or N; n is an integer from 1 to 3; R 1 is a C 3 -C 8 cycloalkyl group, a C 6 -C 10 aryl group, an aliphatic heterocyclic ring or an aromatic heterocyclic ring, or a bicyclic aliphatic saturated hydrocarbon group; R 2 and R 3 , which may be identical or different, are each a hydrogen atom, a lower alkyl group, a lower alkenyl group, a C 3 -C 8 cycloalkyl group, a C 6 -C 10 aryl group, an aromatic heterocyclic ring, or the like; and R 4 is a hydrogen atom, a lower alkyl group, a C 3 -C 6 cycloalkyl group or the like, or a pharmaceutically acceptable salt or ester thereof, and a selective inhibitor against Cdk4 and/or Cdk6 or an anticancer agent containing the compound or a pharmaceutically acceptable salt or ester thereof.
- -
-
Page/Page column 76
(2010/11/25)
-
- 2-PHENYLPYRIDINE DERIVATIVE
-
The present invention relates to a novel 2-phenylpyridine derivative or a salt thereof, wherein the pyridine ring is substituted with a carboxyl group or the like and the benzene ring has an electron-withdrawing group such as a cyano group and an electron-donating group such as a substituted alkoxy group at the same time. Since the compound of the invention has good xanthine oxidase-inhibitory action and uric acid-lowering action and does not have a structure derived from nucleic acid, the compound has advantages of high safety and excellent effects as compared with conventional compounds and is useful as a therapeutic or preventive agent for hyperuricemia, gout, inflammatory bowel diseases, diabetic kidney diseases, diabetic retinopathy, or the like.
- -
-
-
- NOVEL INHIBITORS OF PROTEIN KINASE
-
The present invention relates to novel compounds for inhibition of angiogenesis receptor tyrosine kinases, in particular, VEGF receptor 2 kinase ("KDR") activity, and preparations for preparation of them, and the use of them, and pharmaceutical compositions containing them at a therapeutically effective amount. The compounds according to the present invention are useful for the treatment and prevention of diseases resulting from the undesired KDR activity, for example, angiogenesis-related diseases such as cancers, psoriasis, rheumatoid arthritis, diabetic retinopathy, etc.
- -
-
Page/Page column 52; 63
(2010/11/27)
-
- 2-AMINOQUINAZOLINE DERIVATIVES
-
2-Aminoquinazoline derivatives represented by the general formula (I) or pharmacologically acceptable salts thereof: (I) wherein R1 and R2 are each independently hydrogen, substituted or unsubstituted lower alkyl, or the like; X is a bond or CR7aR7b (wherein R7a and R7b are each independently hydrogen or the like); when X is a bond, R3 is substituted or unsubstituted aryl or a substituted or unsubstituted aromatic heterocyclic group, while when X is CR7aR7b, R3 is substituted or unsubstituted lower alkoxy, substituted or unsubstituted aryl, or the like; R4 is hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or the like; and R5 is hydrogen, substituted or unsubstituted aryl, or the like.
- -
-
Page/Page column 89
(2008/06/13)
-
- Novel scaffolds for beta-helix mimicry
-
Functionalized pyridazine derivatives having a low molecular weight and pharmaceutical compositions thereof are useful as alpha-helix mimetics and for treating conditions and/or disorders mediated by alpha-helix-binding receptors and proteins.
- -
-
Page/Page column 31
(2008/06/13)
-
- PYRIDINE DERIVATIVES AND THEIR USE AS MEDICAMENTS FOR TREATING DISEASES RELATED TO MCH RECEPTOR
-
The present invention encompasses novel substituted pyridine compounds of Formula (I), which act as MCH receptor antagonists. These compositions and pharmaceutical compositions thereof are useful in the prophylaxis or treatment of improving memory function, sleeping and arousal, anxiety, depression, mood disorders, seizure, obesity, diabetes, appetite and eating disorders, cardiovascular disease, hypertension, dyslipidemia, myocardial infarction, binge eating disorders including bulimia, anorexia, mental disorders including manic depression, schizophrenia, delirium, dementia, stress, cognitive disorders, attention deficit disorder, substance abuse disorders and dyskinesias including Parkinson's disease, epilepsy, and addiction.
- -
-
Page/Page column 92-93
(2010/10/20)
-
- P38 MAP kinase inhibitors
-
The present invention relates to compounds of Formula (I) that are p-38 MAP kinase inhibitors, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
- -
-
-
- SUBSTITUTED 3-AMINOQUINUCLIDINES
-
Compounds of the formula STR1 wherein W, Ar 1, Ar 2 and Ar. sup.3 are defined as below; and the pharmaceutically acceptable salts of such compounds.These compounds are substance P antagonists and useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.
- -
-
-
- Palladium(0)-catalyzed heteroarylation of 2- and 3-indolylzinc derivatives. An efficient general method for the preparation of (2-pyridyl)indoles and their application to indole alkaloid synthesis
-
Palladium(0)-catalyzed coupling of (1-(benzenesulfonyl)-2-indolyl)zinc chloride (1) and (1-(tert-butyldimethylsilyl)-3-indolyl)zinc chloride (6) with diversely substituted (alkyl, methoxy, methoxycarbonyl, nitro, hydroxy) 2-halopyridines gives the corresponding 2- and 3-(2-pyridyl)indoles [4 and 7 (or 8), respectively] in excellent yields. A series of other 3-(heteroaryl)indoles (pyrazinyl, furyl, thienyl, indolyl) have been similarly prepared from 6. The potential of some of these (2-pyridyl)indoles in alkaloid synthesis is demonstrated. Thus, from 2-(2-pyridyl)indole 4b, a new synthetic entry to the indolo[2,3-a]quinolizidine system, involving stereoselective hydrogenation of the pyridine ring with subsequent electrophilic cyclization upon the indole 3-position from an appropriately N(b)-substituted 2-(2-piperidyl)indole, is reported. For this purpose, Pummerer cyclizations have been extensively studied. Whereas the indole-unprotected sulfoxide 17 gives the corresponding indoloquinolizidine 19 in low yield and mainly undergoes an abnormal Pummerer cyclization that ultimately leads to sulfide 18, the N(a)-protected sulfoxides 24a and 24b afford the respective indoloquinolizidines 25a,b in 70% yield. On the other hand, the conversion of 3-(2-pyridyl)indole 8k into tetracyclic ketone 35 by stereoselective hydrogenation, followed by cyclization of the resulting all-cis-3-(2-piperidyl)indole 34, represents a formal synthesis of Strychnos alkaloids with the strychnan skeletal type (tubifoline, tubifolidine, 19,20-dihydroakuammicine). A similar conversion of 8j into nordasycarpidone constitutes a formal synthesis of the alkaloids of the uleine group. Reduction of nordasycarpidone leads to tetracycle 37, an advanced intermediate in a previous synthesis of tubotaiwine, a Strychnos alkaloid with the aspidospermatan skeletal type. Finally, piperidylindole 34 was transformed into tetracycle 41, an ABDE substructure of akuammiline alkaloids, by a sequence involving the skeletal rearrangement of an intermediate spiroindolenine as the crucial step.
- Amat, Mercedes,Hadida, Sabine,Pshenichnyi, Grigorii,Bosch, Joan
-
p. 3158 - 3175
(2007/10/03)
-
- Preparation of substituted 2-chloropyridines
-
A process for the preparation of a substituted 2-chloropyridine derivatives of the formula STR1 in which R1, R2, R3 and R4 represent hydrogen or various other radicals, which comprises reacting a pyridine-1-oxide of the formula STR2 with an aromatic carbonyl chloride in the presence of an inert organic solvent and in the presence of an acid acceptor at a temperature between about -20° C. and 200° C.
- -
-
-
- Process for the preparation of substituted 2-chloropyridines
-
A new process has been found for the preparation of substituted 2-chloropyridine derivatives of the formula (I) STR1 wherein R1 to R4 have the meanings as defined in the description. The new process is characterized in that pyridine 1-oxides of the formula II STR2 are reacted with a chlorine-containing phosphoric acid derivative from the series of the chlorophosphoric esters and chlorophosphoramides in the presence of an inert organic solvent and in the presence of an acid acceptor at temperatures between -20° C. and 200° C., and the resulting product is separated further, if appropriate. Compound (I) is known as an intermediate product for medicaments (cf.DE-A 2,812,585) or for insecticidel nitromethylene derivatives (cf. EP-A 163,855).
- -
-
-
- Synthesis of 2-Substituted 4-Pyridylpropionates. Part 1. Claisen Condensation Approach
-
A synthesis of methyl 3-(2-methoxy-4-pyridyl)propionate (4), a key intermediate in the synthesis of the potent and long-acting histamine H2-receptor antagonist SK&F 93574 (3), is described.The key steps in the synthesis of compound (4) are a Claisen ester condensation to give the intermediate (16) and a subsequent reduction step to give the ester (4).The reduction was found to be difficult and our investigations are described.In addition, alternative, but unsuccesful, approaches to the desired pyridylpropionate (4) are discussed.
- Adger, Brian M.,Bannister, Robin,Lewis, Norman J.,O'Farrell, Clare
-
p. 2785 - 2790
(2007/10/02)
-