- 2-AZASPIRO[3.4]OCTANE DERIVATIVES AS M4 AGONISTS
-
Provided herein are compounds according to Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, and R7 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) as well as the use of such compounds as M4 receptor agonists.
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Paragraph 0934-0936
(2021/04/17)
-
- 5-OXA-2-AZASPIRO[3.4]OCTANE DERIVATIVES AS M4 AGONISTS
-
Provided herein are compounds according to Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, and R7 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) as well as the use of such compounds as M4 receptor agonists.
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Page/Page column 90-91; 73
(2021/04/17)
-
- Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate
-
Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson’s disease treatment. Fragment hit-derived pyrrolo[2,3-d]pyrimidines underwent optimization using X-ray structures of LRRK2 kinase domain surrogates, based on checkpoint kinase 1 (CHK1) and a CHK1 10-point mutant. (2R)-2-Methylpyrrolidin-1-yl derivative 18 (LRRK2 G2019S cKi0.7 nM, LE 0.66) was identified, with increased potency consistent with an X-ray structure of 18 /CHK1 10-pt. mutant showing the 2-methyl substituent proximal to Ala147 (Ala2016 in LRRK2). Further structure-guided elaboration of 18 gave the 2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino] derivative 32 . Optimization of 32 afforded diastereomeric oxolan-3-yl derivatives 44 and 45 , which demonstrated a favorablein vitroPK profile, although they displayed species disconnects in thein vivoPK profile, and a propensity for P-gp- and/or BCRP-mediated efflux in a mouse model. Compounds 44 and 45 demonstrated high potency and exquisite selectivity for LRRK2 and utility as chemical probes for the study of LRRK2 inhibition.
- Williamson, Douglas S.,Smith, Garrick P.,Mikkelsen, Gitte K.,Jensen, Thomas,Acheson-Dossang, Pamela,Badolo, Lassina,Bedford, Simon T.,Chell, Victoria,Chen, I-Jen,Dokurno, Pawel,Hentzer, Morten,Newland, Samantha,Ray, Stuart C.,Shaw, Terry,Surgenor, Allan E.,Terry, Lindsey,Wang, Yikang,Christensen, Kenneth V.
-
supporting information
p. 10312 - 10332
(2021/07/26)
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- Fused tricyclic derivative as FGFR4 inhibitor
-
The present invention provides a fused tricyclic derivative that is the selective inhibitor of fibroblast growth factor receptor 4 (FGFR4), a pharmaceutical composition containing the compound, a method of making the compound and a method of treating cell proliferative diseases, such as cancer, using the compounds of the invention.
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Paragraph 0933-0938
(2021/05/12)
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- HPK1 ANTAGONISTS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders.
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Paragraph 1014; 1015
(2021/03/19)
-
- 8-substituted styryl xanthine derivative and application thereof
-
The invention discloses an 8-substituted styryl xanthine derivative and application thereof, and particularly relates to a novel 8-substituted styryl xanthine derivative and a pharmaceutical composition containing the compound, and the 8-substituted styryl xanthine derivative can be used as a selective adenosine A2A receptor antagonist. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in preparation of drugs for treating adenosine A2A receptor related diseases, especially Parkinson's disease.
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Paragraph 0268; 0270-0272; 0290; 0292-0295
(2020/05/01)
-
- Nitrogen-containing fused tricyclic derivative and application thereof
-
The invention discloses a nitrogen-containing fused tricyclic derivative and application thereof, and particularly relates to a novel nitrogen-containing fused tricyclic derivative and a pharmaceutical composition containing the nitrogen-containing fused tricyclic derivative, and the nitrogen-containing fused tricyclic derivative can be used as a selective adenosine A2A receptor antagonist. The invention also relates to a method for preparing the compound and the pharmaceutical composition and application of the compound and the pharmaceutical composition in preparation of drugs for treating adenosine A2A receptor related diseases, especially Parkinson's disease.
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-
Paragraph 0255; 0257-0259
(2020/05/08)
-
- 3,9-DIAZASPIRO[5.5]UNDECANE COMPOUNDS
-
The present invention covers 3,9-diazaspiro[5.5]undecane compounds of general formula (I) and general formula (I-a), in which R1, R2, R3 and R4 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and/or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.
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Page/Page column 437
(2020/04/09)
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- PYRAZOLOPYRIDINE DERIVATIVE HAVING GLP-1 RECEPTOR AGONIST EFFECT
-
The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.
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Paragraph 0410-0413
(2019/08/02)
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- ALKENE COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
-
The present invention provides compounds of Formula (I): Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of famesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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Page/Page column 102
(2019/05/22)
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- ALKENE SPIROCYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
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The present invention provides compounds of Formula (I), or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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Page/Page column 67
(2019/05/22)
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- FUSED RING PYRIMIDINE COMPOUND, INTERMEDIATE, AND PREPARATION METHOD, COMPOSITION AND USE THEREOF
-
Disclosed area fused ring pyrimidine compound, and an intermediate, a preparation method, a composition and a use thereof. The fused ring pyrimidine compound is a compound as shown in formula I, a tautomer, an enantiomer, a diastereoisomer, a pharmaceutically acceptable salt, a metabolite, a metabolic precursor or a prodrug thereof, wherein the above-mentioned compound is used for the preparation of a medicine for preventing, remitting or treating one or more of immune system diseases, autoimmune diseases, cell proliferative diseases, allergic disorders and cardiovascular diseases, and the compound has a strong inhibitory effect on the Janues kinase, FGFR kinase, FLT3 kinase and Src family kinase.
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-
Paragraph 0233-0234
(2018/08/12)
-
- N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicine for treating diabetes
-
The invention discloses an N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicines for treating diabetes. The structural formula of the derivative is as shown in the specification, and in the formula, R1 is halogen or C1-C4 alkyl; R2 is substituted aryl; R3 is H or acyl with 1-4 atoms. The compound disclosed by the invention has functions of remarkably reducing blood sugar and promoting discharge of glucose from urea, and can be used for preparing medicines for treating diabetes.
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Paragraph 0121; 0122; 0123
(2017/07/18)
-
- Stereocontrolled C(sp3)-P bond formation with non-activated alkyl halides and tosylates
-
The C(sp3)-P bond is formed via the reaction between P-H compounds and non-activated alkyl electrophiles, especially secondary alkyl halides and tosylates. This reaction proceeds via an SN2 mechanism with inversion of configuration, so it can be used to form C-P bonds with stereocontrol from chiral secondary alcohols.
- Yang, Chu-Ting,Han, Jun,Liu, Jun,Li, Yi,Zhang, Fan,Gu, Mei,Hu, Sheng,Wang, Xiaolin
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p. 24652 - 24656
(2017/07/11)
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- QUINOLINE AND QUINAZOLINE COMPOUNDS
-
In some embodiments, the invention relates to quinazoline and quinoline compounds of Formula I: (I) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to quinazoline and quinoline compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders.
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-
Paragraph 00248
(2016/05/02)
-
- FUSED HETEROCYCLIC COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTCIAL COMPOSITION, AND USES THEREOF
-
Disclosed are a fused heterocyclic compound, a preparation method therefor, a pharmaceutical composition, and uses thereof. The fused heterocyclic compound is shown in formula I, formula II, or formula III. The preparation method of the fused heterocyclic compound and/or the pharmaceutically acceptable salt thereof in the present invention comprises three synthesizing routes. The present invention also provides a pharmaceutical composition of the fused heterocyclic compound, the pharmaceutical composition containing one or more of the fused heterocyclic compound shown in formula I, formula II, or formula III, the pharmaceutically acceptable salt thereof, hydrates, solvent compounds, polymorphs and prodrugs thereof, and a pharmaceutically acceptable carrier. The present invention also relates to an application of the fused heterocyclic compound and/or the pharmaceutical composition in preparing kinase inhibitors and in preparing drugs for preventing and treating diseases related to kinase. The fused heterocyclic compound of the present invention has selective inhibition function on PI3Kδ, and can be used for preparing drugs for preventing and treating cell proliferation diseases such as cancers, infections, inflammations, or autoimmune diseases.
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-
Paragraph 0317; 0318; 0325; 0326
(2016/09/26)
-
- Glucopyranosyl derivative and application thereof in medicines
-
The invention relates to a glucopyranosyl derivative used as a sodium-dependent glucose transporter (SGLT) inhibitor, a medicinal composition containing the derivative, and an application of the derivative and the medicinal composition in medicines, and especially relates to the glucopyranosyl derivative represented by formula (I) or a pharmaceutically acceptable salt or all stereoisomers thereof, or the medicinal composition containing the derivative, and a use of the derivative and the medicinal composition in the preparation of medicines for treating diabetes and diabetes related diseases.
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Paragraph 0255; 0257; 0258; 0259
(2016/10/08)
-
- 1,3-THIAZOL-2-YL SUBSTITUTED BENZAMIDES
-
The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.
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Page/Page column 144
(2016/07/05)
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- NEW POSITIVE ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTOR
-
The present invention relates to indole derivatives useful in therapy, to compositions comprising said compounds, and to methods of treating diseases comprising administration of said com- pounds. The compounds referred to are positive allosteric modulators (PAMs) of the nicotinic acetylcholine α7 receptor.
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Page/Page column 42
(2014/04/17)
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- NEW INDANYLOXYDIHYDROBENZOFURANYLACETIC ACIDS
-
The present invention relates to compounds of general formula I, wherein the groups R1, R2 and m are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.
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-
Paragraph 0453; 0458
(2013/10/07)
-
- NEW INDANYLOXYDIHYDROBENZOFURANYLACETIC ACID DERIVATIVES AND THEIR USE AS GPR40 RECEPTOR AGONISTS
-
The present invention relates to compounds of general formula I, (I), wherein the groups R1, R2 and m are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.
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Page/Page column 81
(2013/10/21)
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- NEW INDANYLOXYDIHYDROBENZOFURANYLACETIC ACID DERIVATIVES AND THEIR USE AS GPR40 RECEPTOR AGONISTS
-
The present invention relates to compounds of general formula (I), wherein the groups R1, R2 and m are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.
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Page/Page column 101
(2013/10/21)
-
- INDANYLOXYPHENYLCYCLOPROPANECARBOXYLIC ACIDS
-
The present invention relates to compounds of general formula I, wherein the groups R1, R2, R3, m and n are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.
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-
Paragraph 0484
(2014/01/07)
-
- NEW INDANYLOXYPHENYLCYCLOPROPANECARB OXYLIC ACIDS
-
The present invention relates to compounds of general formula I, (I) wherein the groups R1, R2, R3, m and n are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.
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Page/Page column 82; 83
(2014/01/07)
-
- Pyrimidine compounds and methods of making and using same
-
Disclosed herein are pyrimidinyl compounds that are contemplated to be modulators of cystic fibrosis transmembrane regulators (CFTR), and methods of making and using same. Also provided are pharmaceutical compositions and methods of treating disorders associated with cystic fibrosis transmembrane regulators, such as airway inflammation, cystic fibrosis, and the like.
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Page/Page column 79-80
(2013/02/27)
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- NOVEL CARBOXAMIDE DERIVATIVES AS HIV INHIBITORS
-
The present invention relates to carboxamide derivatives of Formula (I), where B1, B2, X, L, n, R, R1, R2, Z1, Z2, Rx and Ry are as defined in the claims, as compounds and compositions for inhibiting Human Immunodeficiency Virus (HIV) and process for making the compounds.
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Page/Page column 36
(2011/06/19)
-
- N-heterocyclic carbene-catalyzed oxidative esterification reaction of aldehydes with alkyl halides under aerobic conditions
-
An efficient N-heterocyclic carbene-catalyzed oxidative esterification reaction of aldehydes with alkyl halides or alkyl 4-methylbenzenesulfonate is reported. It was worth noting that (1) the configuration of alkyl halides or alkyl 4-methylbenzenesulfonates was inverted completely, and (2) the presence of oxygen was crucial for this transformation. The reaction proceeded smoothly under mild conditions and various esters were afforded in moderate to good yields. In addition, we have developed an efficient tandem oxidation/ esterification reaction of alcohols. This methodology provides a rare example of a reaction of the Breslow intermediate to sp3-carbon centered electrophiles. An efficient oxidative esterification reaction of aldehydes with alkyl halides or alkyl 4-methylbenzenesulfonates catalyzed by N-heterocyclic carbenes is reported. Oxygenwas crucial for the reaction, and the configuration of alkyl 4-methylbenzenesulfonate was completely inverted. Copyright
- Xin, Yang-Chun,Shi, Shi-Hui,Xie, Dong-Dong,Hui, Xin-Ping,Xu, Peng-Fei
-
scheme or table
p. 6527 - 6531
(2011/12/22)
-
- AN OXIME DERIVATIVE AND PREPARATIONS THEREOF
-
The problem of the present invention is to provide a useful compound as a glucokinase activating agent, which is the oxime derivative of the formula [I]: wherein Ring A is aryl or heteroaryl; Q is cycloalkyl, heterocycle, alkyl or alkenyl; Ring T is heteroaryl or heterocycle; R1 and R2 are independently hydrogen atom, halogen atom, cycloalkylsulfonyl or the like; R3 and R4 are independently hydrogen atom, hydroxy, oxo, halogen atom or the like; R5 is hydrogen atom, halogen atom, cyano, nitro, tetrazolyl or the like; or a pharmaceutically acceptable salt thereof.
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Page/Page column 68
(2008/06/13)
-
- 3-AMINOPYRROLIDINES AS INHIBITORS OF MONOAMINE UPTAKE
-
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful for the inhibition of the uptake of one or more physiologically active monoamines (serotonin, norepinephrine, and dopamine).
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Page/Page column 117
(2008/06/13)
-
- Pyrrolopyrimidines as therapeutic agents
-
Chemical compounds having structural formula I and physiologically acceptable salts and metabolites thereof, are inhibitors of serine/threonine and tyrosine kinase activity. Several of the kinases, whose activity is inhibited by these chemical compounds, are involved in immunologic, hyperproliferative, or angiogenic processes. Thus, these chemical compounds can ameliorate disease states where angiogenesis or endothelial cell hyperproliferation is a factor. These compounds can be used to treat cancer and hyper proliferative disorders, rheumatiod arthritis, disorders of the immune system, trasplant refections and imflammatory disorders.
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-
-
- SYNTHESIS OF CHIRAL SULFONYLMETHYL ISOCYANIDES, AND COMPARISON OF THEIR PROPENSITIES IN ASYMMETRIC INDUCTION REACTIONS WITH ACETOPHENONES
-
Seven chiral analogues of tosylmethyl isocyanide (TosMIC) were synthesized in order to investigate and compare their ability to achieve asymmetric induction in base mediated reactions with acetophenone and trifluoracetophenone.Acid hydrolysis of the intermediate 2-oxazolines (10 and 11) gave optically active α-hydroxy aldehydes (12 and 13).
- Hundscheid, Frans J. A.,Tandon, Vishnu K.,Rouwette, Pieter H. F. M.,Leusen, Albert M. van
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p. 5073 - 5088
(2007/10/02)
-