- PYRAZOLO[1,5-A]PYRIMIDINE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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The present invention relates to pyrazolopyrimidine derivatives having dual pharmacological activity towards both the α2δ subunit of the voltage-gated calcium channel and the sigma-1 (σ1) receptor, to processes of preparation of such compounds,
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Page/Page column 182-183
(2021/12/08)
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- Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation
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Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds (7 and 10) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies.
- Di Martino, Rita Maria Concetta,Bottegoni, Giovanni,Seghetti, Francesca,Russo, Debora,Penna, Ilaria,De Simone, Alessio,Ottonello, Giuliana,Mandrup Bertozzi, Sine,Armirotti, Andrea,Bandiera, Tiziano,Belluti, Federica,Cavalli, Andrea
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supporting information
p. 949 - 954
(2020/05/04)
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- MULTI-KINASE INHIBITOR COMPOUND, AND CRYSTAL FORM AND USE THEREOF
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The present invention relates to a compound as represented by formula (I) or a pharmaceutically acceptable salt and stereoisomer thereof, wherein R1, R2, X, Y, P, W, and Ar are as defined in the description. The compound of formula (I) of the present invention can be used in the preparation of a drug for treating cancers mediated by abnormality of multi-kinases. Also provided is a crystal form I of a compound 4-(5-(2-chlorophenyl)-3-methyl-2,10-dihydropyrazolo[4,3-b]pyrido[4,3-e][1,4]diazepin-8-yl)morpholine, wherein in an X-ray powder diffraction pattern of crystal form I, there are characteristic peaks at 7.4±0.20, 17.9±0.2°, 18.9±0.2°, 19.4±0.2°, 21.5±0.2°, and 23.7±0.2°.
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Paragraph 0155; 0156
(2019/02/19)
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- Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR
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Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepa
- Zhang, Qiumeng,Shen, Qianqian,Gao, Lixin,Tong, Linjiang,Li, Jia,Chen, Yi,Lu, Wei
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p. 428 - 441
(2018/09/22)
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- A class of pyrazolopyrimidine diazepine derivatives with antitumor effect
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The present invention relates to the field of medicine, wherein a pyrazolopyrimidine diazepine derivative represented by a formula I can significantly inhibit three targets such as Aurora A, Aurora Band vascular endothelial growth factor receptor 2 (VEGFR2/KDR), or two or one of the three targets, and the pharmacological experiment results show that the pyrazolopyrimidine diazepine derivative hassignificant antitumor activity, can be used to be developed into antitumor drugs for treatment or control of malignant tumors, especially drugs for treatment or control of gastric cancer, liver cancer, lung cancer, breast cancer, colon cancer and the like. The formula I is defined in the specification.
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Paragraph 0051; 0053-0056
(2019/01/08)
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- 3 -AMINO- PYRAZOLE DERIVATIVES USEFUL AGAINST TUBERCULOSIS
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A compound of Formula (I) or a pharmaceutically acceptable salt thereof: Wherein: Het is a 5 to 10-membered heteroaromatic ring; Either X is N and Y is CR5; or X is C and Y is S; Z is selected from N and CH; R1 is selected from H and C1-2alkyl; R2 is selected from H, C1-2alkyl, OH, —CH2OH and C1-2alkoxy; Each R3 is independently selected from OH, C1-3alkyl, F, Cl, Br, NH2, and C1-3alkoxy; R4 is selected from C1-3alkyl and haloC1-3alkyl; R5 is selected from H, C1-3alkyl and haloC1-3alkyl; R6 and R7 are either i) each independently selected from H, C1-3alkyl and C1-3alkoxy; or ii) R6 and R7 together with the ring to which they are attached form a 9-membered bicyclic ring; p is 0-3; and RA is selected from H and C1-3alkyl, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Paragraph 0226; 0227; 0228; 0229
(2013/08/15)
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- 3 -AMINO- PYRAZOLE DERIVATIVES USEFUL AGAINST TUBERCULOSIS
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A compound of Formula (I) or a pharmaceutically acceptable salt thereof: (I), Wherein: Het is a 5 to 10-membered heteroaromatic ring; Either X is N and Y is CR5; or X is C and Y is S; Z is selected from N and CH; R1 is selected from H and C1-2alkyl; R2 is selected from H, C1-2alkyl, OH, -CH2OH and C1-2alkoxy; Each R3 is independently selected from OH, C1-3alkyl, F, Cl, Br, NH2, and C1-3alkoxy; R4 is selected from C1-3alkyl and haloC1-3alkyl; R5 is selected from H, C1-3alkyl and haloC1-3alkyl; R6 and R7 are either i) each independently selected from H, C1-3alkyl and C1-3alkoxy; or ii) R6 and R7 together with the ring to which they are attached form a 9-membered bicylic ring; p is 0-3; and RA is selected from H and C1-3alkyl, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Page/Page column 26
(2012/05/04)
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- Diamino pyrazols, their synthesis, keratin fibre dyeing compositions containing them, keratin fibre dyeing methods
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PCT No. PCT/FR97/00750 Sec. 371 Date May 7, 1999 Sec. 102(e) Date May 7, 1999 PCT Filed Apr. 25, 1997 PCT Pub. No. WO97/42173 PCT Pub. Date Nov. 13, 1997The invention discloses new 5-substituted 3,4-diamino pyrazols, their methods of preparation, composit
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