- Amino pyrimidine compound and preparation method and application thereof
-
The invention relates to an amino pyrimidine compound and a preparation method and application thereof. The amino pyrimidine compound has a structure as shown in a formula I. The formula is shown in the description. The compound is an inhibitor of an epidermal growth factor receptor (EGFR) kinase. The invention further relates to a medicine composition comprising the compound, a preparation methodand application thereof in preparation of anti-tumor medicines.
- -
-
Paragraph 0546; 0555; 0556; 0557
(2018/11/22)
-
- Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists
-
Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays a role in metabolic and CNS disorders. The modeling-supported design, synthesis and multi-parameter optimization (biological activity, solubility, metabolic stability, hERG) of novel quinazoline derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified. Clusters of refined hMCHR1 homology models derived from the X-ray structure of the β2-adrenergic receptor, including extracellular loops, were developed and used to guide the design.
- Sasmal, Sanjita,Balaji, Gade,Kanna Reddy, Hariprasada R.,Balasubrahmanyam,Srinivas, Gujjary,Kyasa, Shivakumar,Sasmal, Pradip K.,Khanna, Ish,Talwar, Rashmi,Suresh,Jadhav, Vikram P.,Muzeeb, Syed,Shashikumar, Dhanya,Harinder Reddy,Sebastian,Frimurer, Thomas M.,Rist, ?ystein,Elster, Lisbeth,H?gberg, Thomas
-
scheme or table
p. 3157 - 3162
(2012/06/04)
-
- Discovery of a tetrahydropyrimidin-2(1 H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor
-
Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo[1,5-c]imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. To address this issue, our synthetic efforts were focused on modification of the imidazo[1,5-c] imidazol-3-one moiety of the active metabolite 3a, derived from 1, which resulted in the discovery of the tetrahydropyrimidin-2(1H)-one derivative 5k as a highly potent and selective FXa inhibitor. Compound 5k showed no detectable amide bond cleavage in human liver microsomes, exhibited a good pharmacokinetic profile in monkeys, and had a potent antithrombotic efficacy in a rabbit model without prolongation of bleeding time. Compound 5k is currently under clinical development with the code name TAK-442.
- Fujimoto, Takuya,Imaeda, Yasuhiro,Konishi, Noriko,Hiroe, Katsuhiko,Kawamura, Masaki,Textor, Garret P.,Aertgeerts, Kathleen,Kubo, Keiji
-
experimental part
p. 3517 - 3531
(2010/09/10)
-
- BIARYL-SUBSTITUTED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
-
Biaryl-substituted tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions media
- -
-
Page/Page column 21
(2008/12/08)
-
- High-yielding syntheses of 1-piperidin-4-yl butyro- and valerolactams through a tandem reductive animation-lactamization (reductive lactamization)
-
We report a procedure for the concise and high-yielding syntheses of 1-piperidin-4-yl-substituted butyro- and valero-lactams. Beginning with 1-benzyl-4-piperidone and γ- or δ-amino esters or acids, we have effected a tandem reductive animation lactamizati
- Mapes, Christopher M.,Mani, Neelakandha S.
-
supporting information
p. 482 - 486
(2012/12/31)
-
- Synthesis of substituted 4(Z)-(methoxyimino)pentyl-1-piperidines as dual NK1/NK2 inhibitors
-
The NK1 and NK2 receptor activity of a series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)-4(Z)- (methoxyimino)pentyl-1-piperidines was evaluated. Compounds 11d, 11e, 11f, 12a, and 12k were found to be our most potent inhibitors.
- Ting, Pauline C,Lee, Joe F,Anthes, John C,Shih, Neng-Yang,Piwinski, John J
-
p. 491 - 494
(2007/10/03)
-
- CARBOXAMIDE DERIVATIVES FOR TREATING ASTHMA
-
The present invention concerns novel carboxamide derivatives of formula I, set out hereinbelow which antagonize the pharmacological actions of one of the endogenous neuropeptide tachykinins at the neurokinin 2 (NK2) receptor, making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the novel carboxamide derivatives for use in such treatment, methods for their use, and processes and intermediates for the manufacture of the novel carboxamide derivatives. STR1
- -
-
-
- CARBOXAMIDE DERIVATIVES
-
The present invention concerns novel carboxamide derivatives of formula I, STR1 wherein R 1, R 2, J, m, and M have any of the values defined in the specification, which antagonize the pharmacological actions of one of the endogenous neuropeptide tachykini
- -
-
-