- TRICYCLIC INHIBITORS OF THE BCL6 BTB DOMAIN PROTEIN-PROTEIN INTERACTION AND USES THEREOF
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The present application relates to compounds of Formula (I) or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting interactions with BCL6 BTB, such as cancer.
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Paragraph 00321
(2019/07/13)
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- Amino pyrimidine compound and preparation method and application thereof
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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.
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Paragraph 0165; 0168; 0169; 0170
(2018/11/22)
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- BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION
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The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto- temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
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Paragraph 0132
(2017/02/24)
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- Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer
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After a high-throughput screening campaign identified thioether 1 as an antagonist of the nuclear androgen receptor, a zone model was developed for structure-activity relationship (SAR) purposes and analogues were synthesized and evaluated in a cell-based luciferase assay. A novel thioether isostere, cyclopropane (1S,2R)-27, showed the desired increased potency and structural properties (stereospecific SAR response, absence of a readily oxidized sulfur atom, low molecular weight, reduced number of flexible bonds and polar surface area, and drug-likeness score) in the prostate-specific antigen luciferase assay in C4-2-PSA-rl cells to qualify as a new lead structure for prostate cancer drug development.
- Johnson, James K.,Skoda, Erin M.,Zhou, Jianhua,Parrinello, Erica,Wang, Dan,O'Malley, Katherine,Eyer, Benjamin R.,Kazancioglu, Mustafa,Eisermann, Kurtis,Johnston, Paul A.,Nelson, Joel B.,Wang, Zhou,Wipf, Peter
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supporting information
p. 785 - 790
(2016/08/24)
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- 5-[(PIPERAZIN-1-YL)-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS INHIBITORS FOR THE TREATMENT OF OSTEOARTHRITIS
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The present invention discloses compounds according to Formula (I), wherein R, R2, R3a, R3b, and Cy are as defined herein. The present invention discloses compounds inhibiting ADAMTS, methods for their production, pharmaceutical compositions comprising the same and methods for the prophylaxis and/or treatment of inflammatory conditions and/or diseases involving degradation of cartilage and/or disruption of cartilage homeostasis.
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Paragraph 0196
(2016/07/27)
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- Quinazolinone PARP-1 inhibitors, medicinal composition containing inhibitors, and antitumor use of inhibitors
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The invention discloses quinazolinyl-2,4(1H,3H)-dione PARP-1 inhibitors, and a preparation method, a medicinal composition and a use thereof. The invention concretely relates to quinazolinyl-2,4(1H,3H)-dione derivatives represented by general formula I, a medicinal salt and a preparation method thereof, a composition containing one or more of the compounds, and a use of the compounds in the preparation of tumor prevention and/or treatment medicines.
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Paragraph 0218; 0219; 0220
(2016/10/08)
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- NOVEL COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) inhibitory activity, isomers thereof, or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions comprising the same, a method of treating disease using the composition, and methods for preparing the novel compounds. The novel compounds according to the present invention have histone deacetylase 6 (HDAC6) inhibitory activity, and are effective for the prevention or treatment of HDAC6-associated diseases, including cancer, inflammatory diseases, autoimmune diseases, neurological diseases and neurodegenerative disorders.
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Paragraph 2035; 2036
(2015/10/05)
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- COMPOUND FOR INHIBITING TYPE 5 PHOSPHODIESTERASE AND PREPARATION METHOD THEREOF
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The present invention discloses a compound of formula (I) and citrate thereof as type 5 phosphodiesterase inhibitor, a preparation method thereof, and a pharmaceutical composition including the compound of formula (I) and citrate thereof. The experimental results of the present invention prove that the compound of formula (I) and citrate thereof can inhibit activity of type 5 phosphodiesterase, and can be used for treating erectile dysfunction, inhibiting platelet aggregation and treating thrombosis, decreasing pulmonary hypertension and treating cardiovascular diseases, treating asthma and treating diabetes gastroparesis.
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Paragraph 0016; 0024; 0025
(2013/05/22)
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- COMPOUND FOR INHIBITING TYPE 5 PHOSPHODIESTERASE AND PREPARATION METHOD THEREOF
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The present invention discloses a compound of formula (I) and citrate thereof as type 5 phosphodiesterase inhibitor, a preparation method thereof, and a pharmaceutical composition including the compound of formula (I) and citrate thereof. The experimental results of the present invention prove that the compound of formula (I) and citrate thereof can inhibit activity of type 5 phosphodiesterase, and can be used for treating erectile dysfunction, inhibiting platelet aggregation and treating thrombosis, decreasing pulmonary hypertension and treating cardiovascular diseases, treating asthma and treating diabetes gastroparesis.
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Paragraph 0024; 0025
(2013/05/21)
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- PEPTIDE DEFORMYLASE INHIBITORS
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The present invention is directed to certain {2-(alkyl)-3-[2-(5-fluoro-4-pyrimidinyl)hydrazino]-3-oxopropyl}hydroxyformamide derivatives, compositions containing them, the use of such compounds in the inhibition of bacterial peptide deformylase (PDF) activity, and in the treatment of bacterial infections. Specifically, the invention is directed to compounds of formula (I), wherein R1, R2 and R3 are defined herein and to pharmaceutically acceptable salts thereof. The compounds of this invention are bacterial peptide deformylase inhibitors and can be useful in the treatment of bacterial infections.
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Page/Page column 187
(2009/06/27)
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- N-BENZYL,N'-ARYLCARBONYLPIPERAZINE DERIVATIVES
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The present invention relates to N-benzyl,N′-arylcarbonylpiperazine derivatives having the general formula I to pharmaceutical compositions comprising the same, and to the use of a these N-benzyl,N′-arylcarbonylpiperazine derivatives for the manufacture o
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Page/Page column 32
(2009/10/30)
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- 2-AMINOBENZOXAZOLE CARBOXAMIDES AS 5HT3 MODULATORS
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Compounds of formulae I, II and III: are disclosed as 5-HT3 inhibitors. The compounds are useful in treating CINV, IBS-D and other diseases and conditions.
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Page/Page column 17
(2008/12/04)
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- A NEW CLASS OF HISTONE DEACETYLASE INHIBITORS
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New histone deacetylase inhibitors according to the general formula (I) wherein: Q is a bond, CH2, CH-NR3R4, NR5 or oxygen, X is CH or nitrogen, Y is a bond, CH2, oxygen or NR6, Z is CH or
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Page/Page column 54
(2008/06/13)
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- PHARMACEUTICAL COMPOUNDS
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Fused pyrimidines of formula (I); wherein A represents a thiophene or furan ring; n is 1 or 2; R1 is a group of formula (II); wherein m is 0 or 1; R30 is H or C1-C6 alkyl; R4 and R5 form, together with the N atom to which they are attached, a 5- or 6-membered saturated N-containing heterocyclic group which includes 0 or 1 additional heteroatoms selected from N, S and O, which may be fused to a benzene ring and which is unsubstituted or substituted; or one of R4 and R5 is alkyl and the other is a 5- or 6-membered saturated N-containing heterocyclic group as defined above or an alkyl group which is substituted by a 5- or 6-membered saturated N-containing heterocyclic group as defined above; R2 is selected from formula (a); wherein R6 and R7 form, together with the nitrogen atom to which they are attached, a morpholine, thiomorpholine, piperidine, piperazine, oxazepane or thiazepane group which is unsubstituted or substituted; and formula (b); wherein Y is a C2-C4 alkylene chain which contains, between constituent carbon atoms of the chain and/or at one or both ends of the chain, 1 or 2 heteroatoms selected from O, N and S, and which is unsubstituted or substituted; and R3 is an indazole group which is unsubstituted or substituted; and the pharmaceutically acceptable salt thereof have activity as inhibitors of P13K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with P13 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.
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Page/Page column 50-51
(2008/06/13)
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- FKBP inhibitors
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Compounds of formula (I), their salts and solvates, wherein the substituents are as described herein, are FKBP inhibitors.
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- Piperazine imidazo[1,5-a]quinoxaline ureas as high-affinity GABA(A) ligands of dual functionality
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A series of imidazo[1,5-a]quinoxaline piperazine ureas appended with a tert-butyl ester side chain at the 3-position was developed. Analogues within this series have high affinity for the γ-aminobutyric acid A (GABA(A))/benzodiazepine receptor complex with efficacies ranging from inverse agonists to full agonists. Many analogues were found to be partial agonists as indicated by [35S]TBPS and Cl- current ratios. Uniquely, a number of these analogues were found to have a bell-shaped dose-response profile in the α1β2γ2 subtype as determined by whole cell patch-clamp technique, where in vitro efficacy was found to decrease with increasing drug concentration. Many of the compounds from this series were effective in antagonizing metrazole-induced seizures, consistent with anticonvulsant and possibly anxiolytic activity. Additionally, several analogues were also effective in lowering cGMP levels (to control values) after applied stress, also consistent with anxiolytic-like properties. The most effective compounds in these screens were also active in animal models of anxiety such as the Vogel and Geller assays. The use of the piperazine substituent allowed for excellent drug levels and a long duration of action in the central nervous system for many of the quinoxalines, as determined by ex vivo assay. Pharmacokinetic analysis of several compounds indicated excellent oral bioavailability and a reasonable half-life in rats. From this series emerged two partial agonists (55, 91) which had good activity in anxiolytic models, acceptable pharmacokinetics, and minimal benzodiazepine-type side effects.
- Jacobsen, E. Jon,Stelzer, Lindsay S.,TenBrink, Ruth E.,Belonga, Kenneth L.,Carter, Donald B.,Im, Haesook K.,Im, Wha Bin,Sethy, Vimala H.,Tang, Andy H.,VonVoigtlander, Philip F.,Petke, James D.,Zhong, Wei-Zhu,Mickelson, John W.
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p. 1123 - 1144
(2007/10/03)
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- Konstitutionsisomerie in Polykondensaten. Teil VI. Synthese und Eigenschaften von voellig geordneten und ungeordneten Bipolymaiden aus cis-2,6-Dimethylpiperazin und 1,2,5-Thiadiazol-3,4-dicarbonyl-dichlorid
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The synthesis of constitutionally perfectly regular and random alternating copolyamides from the 'symmetric' monomer 1,2,5-thiadiazol-3,5-dicarbonyl dichloride (4) and the 'non-symmetric' monomer cis-2,6-dimethylpiperazine (7) by solution and interfacial polycondensation methods is described.Their constitutional regularities (s values) were determined by high-resolution 13C-NMR spectroscopy in CDCl3 solutions.Ordered and random copolyamides were amorphous with Tg values of ca. 200 deg C.However, the regular head/tail and the random copolyamides with low molecular weights could be partially crystallized by annealing and showed large differences in their melting points (54 deg C).Beside other physical properties, the membrane properties of the copolyamides were carefully investigated.In H2O desalination by reverse osmosis, no difference in salt rejections and permeabilities between constitutionally regular and random copolyamides were found (within experimental error).In contrast, the regular head/head/tail/tail- and head/tail-type copolyamides showed considerably larger seperation factors in the gas seperation (methane/hydrogen) than the random ones.
- Muehlebach, Andreas,Pino, Piero
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p. 839 - 855
(2007/10/02)
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