- METHODS OF MANUFACTURING A BIFUNCTIONAL COMPOUND, ULTRAPURE FORMS OF THE BIFUNCTIONAL COMPOUND, AND DOSAGE FORMS COMPRISING THE SAME
-
The present disclosure relates to ultra-pure forms, polymorphs, amorphous forms, and formulations of N-[(1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl]-6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]pyridazine-3-carboxamide, referred to herein as Compound A: The present disclosure also relates methods of manufacturing and purifying the same, as well as intermediates useful in the synthesis of Compound A. The ultra-pure forms, polymorphs, amorphous forms, and formulations of Compound A can be used as therapeutic agents for the treatment of various diseases and conditions such as cancer.
- -
-
Paragraph 0475
(2021/11/20)
-
- PYRROLIDINE DERIVATIVE
-
The present invention aims to provide a novel compound which has CGRP receptor antagonist activity and which is useful for the treatment of various diseases mediated by CGRP receptors. That is, the present invention relates to the pyrrolidine derivatives represented by the following formula (I) or a pharmaceutically acceptable salt thereof. In the formulae, W is ring, X is a carbon atom or the like, Y1 to Y4 are carbon atoms or the like, and R1 to R7 is alkyl or the like. The compounds of the present invention or a pharmaceutically acceptable salt thereof have an excellent CGRP receptor antagonist activity, and thus are useful as agents for the treatment of various diseases mediated by CGRP receptors.
- -
-
Paragraph 0454
(2019/04/16)
-
- VINYL COMPOUNDS AS FGFR AND VEGFR INHIBITORS
-
FGFR and VEGFR inhibitors are provided, and compounds represented by formula (1) or formula (II) as FGFR and VEGFR inhibitors, pharmaceutically acceptable salts or tautomers thereof are specifically disclosed.
- -
-
Paragraph 0390; 0391
(2018/06/23)
-
- Developing pyridazine-3-carboxamides to be CB2 agonists: The design, synthesis, structure-activity relationships and docking studies
-
Herein, we described the design and synthesis of a series of pyridazine-3-carboxamides to be CB2-selective agonists via a combination of scaffold hopping and bioisosterism strategies. The compounds were subjected to assessment of their potential activities through calcium mobilization assays. Among the tested derivatives, more than half of these compounds exhibited moderate to potent CB2 agonist activity. Six compounds showed EC50 values below 35 nM, and several derivatives also exhibited significantly enhanced potency and high selectivity at the CB2 receptor over the CB1 receptor. Specifically, compound 26 showed the highest CB2 agonist activity (EC50 = 3.665 ± 0.553 nM) and remarkable selectivity (Selectivity Index > 2729) against CB1. In addition, logPs of some representative compounds were measured to display significantly decreased values in comparison with GW842166X. Furthermore, docking simulations were conducted to explain the interaction mode of this series.
- Qian, Hai-Yan,Wang, Zhi-Long,Xie, Xiao-Yu,Pan, You-Lu,Li, Gang-Jian,Xie, Xin,Chen, Jian-Zhong
-
p. 598 - 611
(2017/06/29)
-
- A compression ammonia urea apperception compound of preparation method and in biological and medical application
-
The present invention provides a semicarbazone compound preparation method and application in biomedicine. The compound is a compound of formula (I) or an enantiomer, a diastereomer, a raceme, a pharmaceutically acceptable salt, a crystalline hydrate or a solvate thereof. The compound has the formula shown in the description, wherein X is sulfur or oxygen; R1 and R2 are separately and independently hydrogen and alkyl containing 1-3 carbon atoms or N=CHR 5, wherein R5 is optionally substituted aryl or optionally substituted alkyl; R3 and R4 are separately and independently hydrogen or alkyl containing 1-3 carbon atoms or substituents selected from formulas III, III, IV, and V shown in the description, wherein X1 is sulfur or oxygen. Y, Y1 and Y2 are separately and independently at least one of hydrogen, alkyl containing 1-3 carbon atoms, halogen, hydroxy, methoxy, amino, sulfonic acid group, nitro, carboxyl, thiol, methylamino, ethylamino, dimethylamino or diethylamino; and Z1 is hydrogen, alkyl containing 1-3 carbon atoms, halogen, hydroxy, amino, methylamino, ethylamino, dimethylamino or diethylamino. The semicarbazone compound is applicable to related diseases caused by copper metabolic dysfunction.
- -
-
Paragraph 0179; 0184; 0186
(2017/08/24)
-
- Pyridazine derivative and preparation method and application thereof
-
The invention provides a pyridazine derivative and a pharmaceutically acceptable salt or hydrate of the pyridazine derivative. The compound is an active ligand of a novel cannabinoid II type receptor CB2. The compound and the pharmaceutically acceptable salt or hydrate of the compound generally have high calcium current activity and quite good selectivity for anthropogenic marijuana receptors CB2. The compound is a specificity agonist of the cannabinoid receptor CB2, and can be used for treating, preventing and inhibiting diseases mediated by CB2 receptors. The compound I has the general formula shown in the description.
- -
-
Paragraph 0118; 0119
(2017/02/17)
-
- PRODUCING METHOD OF NITROGEN-CONTAINING ORGANIC COMPOUND
-
A hydrazine-carbon dioxide-binding compound or hydrazine derivatives 2 carbonyl group react with a compound having one or more nitrogen-containing organic for preparing the compounds of relates to method.
- -
-
Paragraph 0308; 0332-0334
(2016/12/01)
-
- Solid-state and solvent-free synthesis of azines, pyrazoles, and pyridazinones using solid hydrazine
-
Azines, pyrazoles, and pyridazinones were isolated as the sole products in high yields (>97%) by grinding solid hydrazine (H3N +NHCO2-) with di-carbonyl compounds or by their reaction in the absence of solvent. Neither catalysts nor additives were needed to promote the reactions. The solid-state and solvent-free reactions proceeded under ambient conditions and did not produce any wastes other than water and carbon dioxide. They are operationally easy, environmentally safe, and readily scalable, allowing for highly selective synthesis of compounds containing the hydrazine motif. Copyright
- Lee, Byeongno,Kang, Philjun,Lee, Kyu Hyung,Cho, Jaeheung,Nam, Wonwoo,Lee, Won Koo,Hur, Nam Hwi
-
supporting information
p. 1384 - 1388
(2013/04/23)
-
- Further studies on 2-arylacetamide pyridazin-3(2H)-ones: Design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists
-
Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and te
- Giovannoni, Maria Paola,Schepetkin, Igor A.,Cilibrizzi, Agostino,Crocetti, Letizia,Khlebnikov, Andrei I.,Dahlgren, Claes,Graziano, Alessia,Dal Piaz, Vittorio,Kirpotina, Liliya N.,Zerbinati, Serena,Vergelli, Claudia,Quinn, Mark T.
-
p. 512 - 528
(2013/07/27)
-
- Solid-state reactivity of the hydrazine-hydroquinone complex
-
The solid-state reactivities of the hydrazine-hydroquinone 1:1 complex and of hydrazine hydrochloride with solid aldehydes, ketones, carboxylic acids, thiohydantoin and 4-nitrophenyl isothiocyanate were investigated. Only the hydrazine complex provides quantitative additions, condensations, ring openings and ring closures. The solid-state mechanisms were investigated by atomic force microscopy (AFM) and the far-reaching anisotropic molecular movements are correlated with the crystal packing, both on the hydrazine complex surface and on the surface of two benzaldehydes. The hydrazine moves into the aldehyde crystals for chemical reaction without melting. Characteristic surface features are created by the common phase rebuilding and phase transformation on both the hydrazine-donating and -accepting crystals. Copyright
- Kaupp, Gerd,Schmeyers, Jens
-
p. 388 - 394
(2007/10/03)
-
- Endothelin receptor antagonists
-
This invention relates to pyridizinone derivatives of formula I STR1 wherein the various substituents are defined in the specification, and salts thereof, which have useful pharmacological properties, in particular endothelin receptor-antagonistic properties. The compounds are thus useful for the treatment of illnesses associated with endothelin activities, such as hypertension, cardiac insufficiency, coronary heart disease, renal, cerebral and myocardial ischaemia, renal insufficiency, cerebral infarct, subarachnoid haemorrhage, arteriosclerosis pulmonary high blood pressure, inflammations, asthma, prostate hyperplasia, endotoxic shock and in complications after the administration of immunosuppressants which produce renal vasoconstriction.
- -
-
-