- Design, synthesis and evaluation of covalent inhibitors of DprE1 as antitubercular agents
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Decaprenylphosphoryl-β-D-ribose 2′-oxidoreductase (DprE1) is a promising drug target for the development of novel anti-tubercular agents, and inhibitors of DprE1 are being investigated extensively. Among them, the 1,3-benzothiazinone compounds such as BTZ
- Liu, Lingfeng,Kong, Chengcheng,Fumagalli, Marco,Savková, Karin,Xu, Yiwen,Huszár, Stanislav,Sammartino, José C.,Fan, Dongguang,Chiarelli, Laurent R.,Miku?ová, Katarína,Sun, Zhaogang,Qiao, Chunhua
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- Substituted pyrazolopyrimidine TAM inhibitor and application thereof
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The invention relates to the technical field of medicines, in particular to a substituted pyrazolopyrimidine TAM inhibitor compound and pharmaceutically acceptable salt, ester or stereoisomer thereof, a pharmaceutical composition containing the compound,
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Paragraph 0270; 0277-0279
(2021/05/08)
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- JNK inhibitor as well as pharmaceutical composition and application thereof
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The invention provides a compound represented by a formula (I), racemates, stereoisomers, tautomers, isotope markers, solvates, polymorphic substances, nitrogen oxides, or pharmaceutically acceptablesalts thereof, and application as a JNK inhibitor. The invention also provides a preparation method of the compound shown in the formula (I), a pharmaceutical composition containing the compound shownin the formula (I), and application of the compound shown in the formula (I) to preparation of a medicine, and the medicine is used for treating diseases which can be treated by inhibiting the activity of JNK.
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Paragraph 0406-0409; 0428-0431
(2021/03/31)
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- Substituted pyrimidine compound, pharmaceutical composition thereof and application of compound
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The invention relates to a substituted pyrimidine compound, a pharmaceutical composition thereof and application of the compound. The substituted pyrimidine compound has excellent inhibitory activityon mutant EGFR and mutant HER2, and has excellent pharma
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Paragraph 0196-0201
(2021/01/24)
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- MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
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This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators.
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Paragraph 001035
(2021/02/19)
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- Nitrogen-containing heterocyclic compound, pharmaceutical composition and application thereof
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The invention provides a nitrogen-containing heterocyclic compound shown as general formula (I) in the specification or a pharmaceutically acceptable salt, solvate, active metabolite, polymorph, isotope label or isomer thereof, and further provides a phar
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Paragraph 0098; 0100-0102
(2020/03/06)
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- Method for synthesizing 2,4-dichloro-5-pyrimidineformyl chloride
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The invention provides a method for synthesizing 2,4-dichloro-5-pyrimidineformyl chloride. The method comprises the synthesis steps: taking uracil-5-formic acid, phosphorous oxychloride and phosphoruspentachloride, performing mixing, performing heating for a reflux reaction, performing cooling after completion of the reflux reaction, evaporating excessive phosphorus oxychloride, and performing reduced pressure distillation so as to obtain the pure product. The commercially-available uracil-5-formic acid is adopted as a raw material, and 2,4-dichloro-5-pyrimidineformyl chloride is generated through one step of chlorination; the starting materials of the reaction have commercial supply of a large amount, and are cheap and easily available, and auxiliary materials can be recycled, so that the cost is reduced significantly, pollution of toxic substances to the environment in the production process is avoided, and the safety during the operation is improved at the same time; and the yieldis improved greatly, the time is shortened effectively, the operation is simple, and the post-treatment process is simplified.
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Paragraph 0018-0032
(2019/11/13)
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- SYNTHESIS OF CERDULATINIB
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The present disclosure provides processes for the preparation of cerdulatinib, which is of formula (I): Formula (I) or a salt thereof. The disclosure also provides intermediates and processes for the preparation of the intermediates useful in the preparation of cerdulatinib or a salt thereof.
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Paragraph 0101
(2019/11/19)
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- PYRAZOLOPYRIMIDINE DERIVATIVES, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR USE IN PREVENTING OR TREATING CANCER, AUTOIMMUNE DISEASE AND BRAIN DISEASE CONTAINING THE SAME AS AN ACTIVE INGREDIENT
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The present invention relates to a pyrazolopyrimidine derivative, a preparation method thereof and a pharmaceutical composition comprising the same as an active ingredient for the prevention or treatment of cancer, autoimmune disease and brain disease. The pyrazolopyrimidine derivative of the present invention exhibits excellent Bruton's tyrosine kinase inhibition activity, so that it can be effectively used as a pharmaceutical composition for the prevention or treatment of cancer, autoimmune disease and Parkinson's disease.
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Paragraph 469-472
(2018/12/02)
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- Atorvastatin that non-preparation method
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The invention relates to a preparation method of avanafil and a new compound provided in a preparation process. According to the method, 5-uracil carboxylic acid or an ester thereof is taken as the raw material, and the avanafil meeting the clinical requirements can be synthesized at a relatively cost; besides, the preparation method is simple and convenient to operate, mild in reaction conditions, high in yield, low in cost, environmentally friendly and suitable for industrial large-scale production of the avanafil.
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- PYRAZOLO[3,4-D]PYRIMIDIN DERIVATIVE AND ITS USE FOR THE TREATMENT OF LEISHMANIASIS
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The compound 3,3,3-trifluoro-N-((1,4-trans)-4-((3-((S)-2-methylmorpholino)-1H- pyrazolo[3,4-d]pyrimidin-6-yl)amino)cyclohexyl)propane-1-sulfonamidehaving the Formula (I) or a salt thereof, its opposite enantiomer, compositions comprising the compound and its use in the treatment or prevention of leishmaniasis, particularly visceral leishmaniasis.
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Page/Page column 38-39
(2016/08/17)
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- INHIBITORS OF ACK1/TNK2 TYROSINE KINASE
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Described are cancer therapies and anti-cancer compounds. In particular, disclosed are ihibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specifc example, compound having Formula I through IV are disclosed.
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Page/Page column 56; 57
(2015/02/25)
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- Development of novel ACK1/TNK2 inhibitors using a fragment-based approach
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The tyrosine kinase ACK1, a critical signal transducer regulating survival of hormone-refractory cancers, is an important therapeutic target, for which there are no selective inhibitors in clinical trials to date. This work reports the discovery of novel and potent inhibitors for ACK1 tyrosine kinase (also known as TNK2) using an innovative fragment-based approach. Focused libraries were designed and synthesized by selecting fragments from reported ACK inhibitors to create hybrid structures in a mix and match process. The hybrid library was screened by enzyme-linked immunosorbent assay-based kinase inhibition and 33P HotSpot assays. Systematic structure-activity relationship studies led to the identification of compound (R)-9b, which shows potent in vitro (IC50 = 56 nM, n = 3, 33P HotSpot assay) and in vivo (IC50 1/2 > 6 h).
- Lawrence, Harshani R.,Mahajan, Kiran,Luo, Yunting,Zhang, Daniel,Tindall, Nathan,Huseyin, Miles,Gevariya, Harsukh,Kazi, Sakib,Ozcan, Sevil,Mahajan, Nupam P.,Lawrence, Nicholas J.
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p. 2746 - 2763
(2015/04/14)
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- SUBSTITUTED NICOTINIMIDE INHIBITORS OF BTK AND THEIR PREPARATION AND USE IN THE TREATMENT OF CANCER, INFLAMMATION AND AUTOIMMUNE DISEASE
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Compounds of Formula I, as shown below and defined herein: and pharmaceutically acceptable salts, syntheses, intermediates, formulations, and methods of treating diseases including cancer, inflammation, and autoimmune disease mediated at least in part by Bruton's Tyrosine Kinase (BTK).
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Page/Page column 55
(2015/04/15)
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- Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors
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5-Carbamoyl-2-phenylpyrimidine derivative 2 has been identified as a phosphodiesterase 4 (PDE4) inhibitor with moderate PDE4B inhibitory activity (IC50 = 200 nM). Modification of the carboxylic acid moiety of 2 gave N-neopentylacetamide derivative 10f, which had high in vitro PDE4B inhibitory activity (IC50 = 8.3 nM) and in vivo efficacy against lipopolysaccharide (LPS)-induced pulmonary neutrophilia in mice (ID50 = 16 mg/kg, ip). Furthermore, based on the X-ray crystallography of 10f bound to the human PDE4B catalytic domain, we designed 7,8-dihydro-6H-pyrido[4,3-d] pyrimidin-5-one derivative 39 which has a fused bicyclic lactam scaffold. Compound 39 exhibited excellent inhibitory activity against LPS-induced tumor necrosis factor alpha (TNF-α) production in mouse splenocytes (IC 50 = 0.21 nM) and in vivo anti-inflammatory activity against LPS-induced pulmonary neutrophilia in mice (41% inhibition at a dose of 1.0 mg/kg, i.t.).
- Goto, Taiji,Shiina, Akiko,Yoshino, Toshiharu,Mizukami, Kiyoshi,Hirahara, Kazuki,Suzuki, Osamu,Sogawa, Yoshitaka,Takahashi, Tomoko,Mikkaichi, Tsuyoshi,Nakao, Naoki,Takahashi, Mizuki,Hasegawa, Masashi,Sasaki, Shigeki
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p. 7025 - 7037
(2013/11/06)
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- PROTEIN KINASE C INHIBITORS AND USES THEREOF
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This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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Page/Page column 29
(2012/02/03)
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- ANTINEOPLASTIC DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
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The disclosure concerns heterobicyclic compounds of general formula (I) and acid addition salts, hydrates and solvates thereof, as well as enantiomers, diastereoisomers and mixtures thereof. Methods for preparing the compounds, pharmaceutical compositions, and methods of treatment also are disclosed.
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Page/Page column 21
(2011/10/19)
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- PROTEIN KINASE C INHIBITORS AND USES THEREOF
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This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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Page/Page column 41
(2011/06/23)
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- NICOTINAMIDE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
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The disclosure relates to compounds of formula (I): wherein A, Z, Z′, L, R2 and R3 are as defined in the disclosure, to compositions comprising said compounds, and to methods for the manufacture and therapeutic use thereof.
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Page/Page column 18
(2010/09/07)
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- A facile synthesis of novel 2-amino-6-arylmethyl-7-carboxamido-7,8- dihydropyrimido[5,4-f][1,4]thiazepin-5-ones
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A facile synthesis of novel 2-amino-6-arylmethyl-7-carboxamido-7,8- dihydropyrimido[5,4-f][1,4]thiazepin-5-ones is described. The synthesis was developed on solid phase and was applied to provide a series of analogs in good yield. The key reactions are acylation of a cysteine derivative with 2,4-dichloropyrimidine-5-carbonyl chloride followed by cyclization to generate a 6-arylmethyl-7-carboxamido-2-chloro-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5- one, which is further derivatized with an amine to give the desired 2-amino-6-arylmethyl-7-carboxamido-7,8-dihydropyrimido[5,4-f][1,4] thiazepin-5-one.
- Qin, Lan-Ying,Cole, Andrew G.,Metzger, Axel,Brescia, Marc-Raleigh,Saionz, Kurt W.,Zhang, Joan J.,Rigollier, Pascal,Wareing, James R.,Gstach, Hubert,Zimmermann, Juerg,Dolle, Roland E.,Baldwin, John J.,Henderson, Ian
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experimental part
p. 4486 - 4489
(2010/10/02)
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- PYRIMIDINECARBOXAMIDE DERIVATIVES AS INHIBITORS OF SYK KINASE
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The compound of formula (I) or a salt, preferably a pharmaceutically acceptable salt, thereof; is an inhibitor of spleen tyrosine kinase (SYK) and therefore potentially of use in treating diseases resulting from inappropriate mast cell activation, for ins
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Page/Page column 31
(2010/09/17)
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- 2-Cyano-pyrimidines: A new chemotype for inhibitors of the cysteine protease cathepsin K
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Starting from the purine lead structure 1, a new series of cathepsin K inhibitors based on a pyrimidine scaffold have been explored. Investigations of P3 and P2 substituents based on molecular modeling suggestions resulted in potent cathepsin K inhibitors
- Altmann, Eva,Aichholz, Reiner,Betschart, Claudia,Buhl, Thomas,Green, Jonathan,Irie, Osamu,Teno, Naoki,Lattmann, René,Tintelnot-Blomley, Marina,Missbach, Martin
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p. 591 - 594
(2007/10/03)
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- SULFOXIMINE-SUBSTITUTED PYRIMIDINES , THEIR PREPARATION AND USE AS DRUGS
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The invention relates to sulfoximine-substituted pyrimidines of the general Formula (I) processes for the preparation thereof and their use as kinase inhibitors for treating for example cancer or inflammation.
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Page/Page column 212-213
(2010/11/27)
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- Sulfoximine-substituted pyrimidines, processes for production thereof and use thereof as drugs
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The invention relates to sulfoximine-substituted pyrimidines of the general formula I processes for the preparation thereof and their use as drugs.
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Page/Page column 87
(2010/11/28)
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- SUBSTITUTED 2-ANILINOPYRIMIDINES AS CELL CYCLE KINASE INHIBITORS OR RECEPTOR TYROSINE KINASE INHIBITORS, PRODUCTION OF SAID SUBSTANCES AND USE OF THE LATTER AS MEDICAMENTS
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The invention relates to pyrimidine derivatives of general formula (I), in which R1, R2, R3, R4, A and D are defined as cited in the description, said derivatives being used as inhibitors of cyclin-dependent kin
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Page/Page column 51
(2010/10/20)
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- 2-AMINO-4-HYDROXY-5-PYRIMIDINECARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF T CELL ACTIVATION FOR THE TREATMENT OF INFLAMMATORY DISEASES
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The present invention relates to pyrimidine or pyridine carboxamides or pharmaceutically-acceptable salts thereof. Also included is a method of treatment of inflammation, inhibition of T cell activation and proliferation, arthritis, rheumatoid arthritis,
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Page/Page column 75-76
(2008/06/13)
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- Macrocyclic pyrimidines, their production and use as pharmaceutical agents
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Macrocyclic pyrimidine derivatives of general formula I in which R1 to R5, X, Y, A, B, m and n have the meanings that are contained in the description, as inhibitors of the cyclin-dependent kinase, their processes for production as well as their use as medications for treating various diseases are described.
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Page column 19-20
(2010/02/08)
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- Pyrimidine derivatives
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Compounds of formula (I), wherein R1, p, R2, q, R3 and R4 are defined within, and a pharmaceutically acceptable salts and in vivo hydrolysable esters are described. Also described are processes for their prepara
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- Pyrimidine carboxamides and related compounds and methods for treating inflammatory conditions
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Compounds having utility as antinflammatory agents in general and, more specifically, for the prevention and/or treatment of immunoinflammatory and autoimmune diseases are disclosed. The compounds are pyrimidine- or pyrazine-containing compounds and, in one embodiment, are carboxyamides of the same. Methods are also disclosed for preventing and/or treating inflammatory conditions by administering to an animal in need thereof an effective amount of a compound of this invention, preferably in the form of a pharmaceutical composition.
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- Quinazoline compounds and antihypertensives
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Disclosed herein is an antihypertensive preparation containing, as an active component, a novel quinazoline derivative represented by the following general formula or a salt thereof: STR1 wherein R100 means a hydrogen atom or methoxy group, R200 and R300 denote individually a hydrogen atom or lower alkoxy group, R400 is a hydrogen atom or amino group, l stands for 2 or 3, and Het is a specific hetero ring group.
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