- Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin
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A series of novel substituted-[(3R)-amino-2-(2,5-difluorophenyl)]tetrahydro-2H-pyran analogs have been prepared and evaluated as potent, selective and orally active DPP-4 inhibitors. These efforts lead to the discovery of a long acting DPP-4 inhibitor, omarigliptin (MK-3102), which recently completed phase III clinical development and has been approved in Japan.
- Chen, Ping,Feng, Dennis,Qian, Xiaoxia,Apgar, James,Wilkening, Robert,Kuethe, Jeffrey T.,Gao, Ying-Duo,Scapin, Giovanna,Cox, Jason,Doss, George,Eiermann, George,He, Huaibing,Li, Xiaohua,Lyons, Kathryn A.,Metzger, Joseph,Petrov, Aleksandr,Wu, Joseph K.,Xu, Shiyao,Weber, Ann E.,Yan, Youwei,Roy, Ranabir Sinha,Biftu, Tesfaye
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Read Online
- Pyrrolopyrazole derivatives and preparation method thereof, and application of pyrrolopyrazole derivatives in medicines
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The invention relates to pyrrolopyrazole derivatives and a preparation method thereof, and application of the pyrrolopyrazole derivatives in medicines. Specifically, the invention relates to novel pyrrolopyrazole derivatives as shown in a general formula (I) in the specification, the preparation method of the pyrrolopyrazole derivatives and application of the pyrrolopyrazole derivatives or pharmaceutical compositions containing the pyrrolopyrazole derivatives as therapeutic agents, particularly as gastric acid secretion inhibitors and potassium ion competitive acid blockers P-CABs) in biological medicines. All the substituents (R1, R2, R3 and R4) and groups (X and Y) in the general formula (I) are as defined in the specification.
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Paragraph 0075-0076
(2021/03/13)
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- Guanidine derivative and application thereof
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The invention relates to a guanidine derivative serving as a VAP-1 inhibitor and application of the guanidine derivative, and further relates to a pharmaceutical composition containing the compound. The compound or the pharmaceutical composition can be us
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Paragraph 0534; 0536-0538
(2020/06/09)
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- BICYCLIC INHIBITORS OF HISTONE DEACETYLASE
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Provided herein are compounds and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of conditions associated with inhibition of HDAC (e.g,. HDAC2).
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Paragraph 0062; 0065; 0075-0076
(2019/02/25)
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- Bicyclic inhibitors of histone deacetylase
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Provided herein are compounds and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of conditions associated with inhibition of HDAC (e.g., HDAC2).
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Page/Page column 14-15
(2018/05/04)
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- Inhibitor for dipeptidyl peptidase-IV
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The invention provides an aminotetrahydropyran derivative with a general formula (I) as described in the specification, pharmaceutically acceptable salts, hydrates, solvates and stereoisomers thereof, a preparation method for the aminotetrahydropyran derivative, and a pharmaceutical composition containing the aminotetrahydropyran derivative. The aminotetrahydropyran derivative provided by the invention can inhibit the activity of dipeptidyl peptidase-IV(DPP-IV), and can be used for treatment of diseases related to dipeptidyl peptidase-IV, especially for treatment of diabetes.
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Paragraph 0105; 0106
(2017/08/28)
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- Aminotetrahydropyrane derivatives and medical applications thereof
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The invention discloses aminotetrahydropyrane derivatives and medical applications thereof. The invention relates to substituted aminotetrahydropyrane with a novel structural formula (I). The substituted aminotetrahydropyrane can be used as an inhibitor of dipeptidyl peptidase-IV, and can be applied to treatment or prevention of diseases related with dipeptidyl peptidase-IV, such as diabetes, especially type II diabetes. The invention also relates to a pharmaceutical composition comprising the aminotetrahydropyrane derivatives, and an application of the compounds and the composition in the treatment or prevention of diseases related with dipeptidyl peptidase-IV.
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Paragraph 0100; 0102; 0102
(2017/08/28)
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- Amino tetrahydropyrane derivatives
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The invention provides amino tetrahydropyrane derivatives, pharmaceutically-acceptable salts, hydrates, solvates, stereoisomers and prodrugs of the amino tetrahydropyrane derivatives, a preparation method of the amino tetrahydropyrane derivatives and a pharmaceutical composition containing the compounds. A formula (I) of the amino tetrahydropyrane derivatives is as shown in the specification. The compounds are capable of inhibiting activity of DPP-IV (dipeptidyl peptidase IV) and can be used for treating dipeptidyl peptidase IV associated diseases such as diabetes, obesity and other metabolic diseases.
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Paragraph 0167-0169
(2017/08/28)
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- AMINOTETRAHYDROPYRAN DERIVATIVE USED AS DIPEPTIDYL PEPTIDASE-IV INHIBITOR
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Provided is an Aminotetrahydropyran derivative represented by general formula (I), a preparation method for the derivative, a pharmaceutical composition containing the derivative, and the use of the derivative to prepare a therapeutic agent, especially a dipeptidyl peptidase-IV inhibitor.
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Paragraph 0085-0086
(2017/04/14)
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- 4,6 DIHYDROPYRROLO [3,4-C] PYRAZOLE-5 (1H)-CARBONITRILE DERIVATES FOR TRATING CANCER
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The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs) and/ or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or
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Page/Page column 73
(2017/10/13)
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- Preparation method for 2-formyl chloride-2,4,5,6-tetrahydropyrrole[3,4-c]pyrazole benzene sulfonate
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The invention discloses a preparation method for 2-formyl chloride-2,4,5,6-tetrahydropyrrole[3,4-c]pyrazole benzene sulfonate. The preparation method comprises the following steps: (1) adding a solvent A and dimethyl formamide-dimethyl adipate (DMF-DMA) i
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Paragraph 0049
(2016/10/07)
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- CARM1 INHIBITORS AND USES THEREOF
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Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R1a, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is a 6-membered monocyclic heteroaryl ring system of Formula: wherein L2, R13, G8, G10, G11, and G12 are as defined herein. Compounds of the present invention are useful for inhibiting CARMl activity. Methods of using the compounds for treating CARMl -mediated disorders are also described.
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Paragraph 00377
(2016/04/09)
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- Aminotetrahydropyran derivative used as dipeptidyl peptidase-IV inhibitor
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The invention provides an aminotetrahydropyran derivative as shown in the general formula (I), pharmaceutically acceptable salt, hydrate, solvate and stereisomer of the derivative, a preparation method thereof, and a pharmaceutical composition containing the compound. The compound can inhibit activity of dipeptidyl peptidase IV (DPP-IV) and can be used in treating diseases related to dipeptidyl peptidase IV.
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Paragraph 0126; 0127
(2016/10/09)
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- Novel Tetrahydropyrido[4,3-d]pyrimidines as Potent Inhibitors of Chaperone Heat Shock Protein 90
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Heat shock protein 90 (Hsp90) is a potential target for oncology therapeutics. Some inhibitors have shown antitumor effects in clinical trials, spurring the discovery of small molecule Hsp90 inhibitors. Here, we describe the structural optimization studies of a hit compound, tetrahydropyrido[4,3-d]pyrimidine-based Hsp90 inhibitor 15, which exhibits inhibitory activity against Hsp90. A series of analogues were synthesized, and their structure-activity and structure-property relationships were analyzed. These explorations led to the discovery of compound 73, which exhibited potent in vitro activities, good physicochemical properties, favorable ADME properties, and a potent antitumor effect in an HCT116 xenograft model. Furthermore, 73 exhibited no ocular toxicity in a rat retinal damage model, suggesting it is a relatively safe Hsp90 inhibitor. As a promising antitumor agent, 73 was progressed for further preclinical evaluation.
- Jiang, Fen,Wang, Hui-Jie,Jin, Yu-Hui,Zhang, Qiong,Wang, Zhi-Hui,Jia, Jian-Min,Liu, Fang,Wang, Lei,Bao, Qi-Chao,Li, Dong-Dong,You, Qi-Dong,Xu, Xiao-Li
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p. 10498 - 10519
(2016/12/16)
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- KINASE INHIBITORS
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The present invention relates to compounds of formulae I and II wherein the variables are as defined herein. These compounds are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
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Paragraph 0308
(2013/09/26)
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- METHOD OF TREATING CONDITIIONS WITH KINASE INHIBITORS
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The present invention relates to a method of treating ophthalmic diseases and conditions, e.g. diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, etc., in a subject comprising administering to said subject a therapeutically effective amount of at least one compound of formula I or a prodrug, pharmaceutically acceptable salt, racemic mixtures or enantiomers of said compound. The compounds of formula I are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
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Paragraph 0292-0293
(2013/09/26)
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- Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of clinical candidate (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2- (methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran- 3-amine (23)
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A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound 23, which is very potent, selective, efficacious in the diabetes PD model, and has an excellent pharmacokinetic profile, is selected as a clinical candidate.
- Biftu, Tesfaye,Qian, Xiaoxia,Chen, Ping,Feng, Dennis,Scapin, Giovanna,Gao, Ying-Duo,Cox, Jason,Sinha Roy, Ranabir,Eiermann, George,He, Huabing,Lyons, Kathy,Salituro, Gino,Patel, Sangita,Petrov, Alexander,Xu, Feng,Xu, Shiyao Sherrie,Zhang, Bei,Caldwell, Charles,Wu, Joseph K.,Weber, Ann E.
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p. 5361 - 5366
(2013/09/23)
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- AMINOTETRAHYDROPYRANS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel substituted aminotetrahydropyrans of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 32
(2010/11/28)
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- Synthesis of the bicyclic secondary amines via dimethylaminomethylene ketones from 3-pyrrolidone and 4-piperidone
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The reaction of N-protected 3-pyrrolidone and 4-piperidone with N,N-dimethylformamide dimethyl acetal gave the dimethylaminomethylene ketones, which reacted with several types of hydrazines, amidines, and guanidine to afford the secondary amines having fused ring system.
- Fukui, Hideto,Inoguchi, Kiyoshi,Nakano, Jun
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p. 257 - 264
(2007/10/03)
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