- NovelN-transfer reagent for converting α-amino acid derivatives to α-diazo compounds
-
A novel universalN-transfer reagent for direct and effective transformation of α-amino ketones, acetamides, and esters to the corresponding α-diazo products under mild basic conditions has been developed. This one-step synthetic approach not only allows for generation of α-substituted-α-diazo carbonyl compounds from α-amino acid derivatives but also permits preparation of α-diazo dipeptides fromN-terminal dipeptides (32 examples, up to 91%).
- Lu, Guan-Han,Huang, Tzu-Chia,Hsueh, Hsiao-Chin,Yang, Shin-Cherng,Cho, Ting-Wei,Chou, Ho-Hsuan
-
p. 4839 - 4842
(2021/05/25)
-
- Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution
-
The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1 alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate electrophiles, while maintaining a high degree of N-1 regioselectivity.
- Alam, Ryan M.,Keating, John J.
-
supporting information
p. 1939 - 1951
(2021/08/23)
-
- Preparation methods of 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine
-
The invention relates to preparation methods of a 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine. The 1H-indazol-3-carboxylic acid derivative is a compound with a structure shown in a formula (1) and a formula (2), and is mainly structurally characterized by having a 1H-indazol-3-carboxylic acid amide skeleton and a 1H-indazol-3-carboxylic ester skeleton. The 1H-indazol-3-carboxylic acid derivative can be synthesized by taking simple o-aminophenylacetic acid amide or o-aminophenylacetic acid ester as an initial raw material. The 1H-indazol-3-carboxylic acid derivative is a key intermediate for synthesizing a plurality of medicines, such as granisetron, lonidamine and the like. The synthesis method of the 1H-indazol-3-carboxylic acid derivative and the drug molecules glassetron and lonidamine is simple, the reaction condition is mild, the reaction speed is high, the yield is high, and purification is easy.
- -
-
Paragraph 0072-0077; 0097-0102; 0122; 0133-0135
(2021/05/12)
-
- NOVEL ARYLALKYL PYRAZOLE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS
-
Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
- -
-
Page/Page column 97-98
(2020/05/21)
-
- Substituted 3-indazole Mcl-1 protein inhibitor as well as preparation method and application thereof
-
The invention discloses a substituted 3-indazole Mcl-1 protein inhibitor as well as a preparation method and application thereof. The compound has a structure represented by a general formula (I) which is described in the specification. The compound discl
- -
-
Paragraph 0029; 0039
(2020/07/28)
-
- EPHA4 CYCLIC PEPTIDE ANTAGONISTS AND METHODS OF USE THEREOF
-
Disclosed herein are compounds and methods of use thereof for the modulation of EphA4 receptor activity. In an aspect, is provided a method of treating or preventing a disease or disorder mediated by EphA4, comprising administering to a subject in need thereof a therapeutically effective amount of a compound as described herein, including certain embodiments, or the structural Formula (I), (l-A), (II), (III), (IV), (IV-1), (V), (Vl-A), (Vl-B), (VII-1), (VII-2), (VIII-1), or (VIII-2), or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
- -
-
Paragraph 0632-0634
(2019/11/19)
-
- Targeting Serotonin 2A and Adrenergic α1 Receptors for Ocular Antihypertensive Agents: Discovery of 3,4-Dihydropyrazino[1,2-b]indazol-1(2H)-one Derivatives
-
Glaucoma affects millions of people worldwide and causes optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and decreasing IOP is the key therapeutic target of current pharmacological treatments. As potential ocular hypotensive agents, we studied compounds that act on two receptors (serotonin 2A and adrenergic α1) linked to the regulation of aqueous humour dynamics. Herein we describe the design, synthesis, and pharmacological profiling of a series of novel bicyclic and tricyclic N2-alkyl-indazole-amide derivatives. This study identified a 3,4-dihydropyrazino[1,2-b]indazol-1(2H)-one derivative with potent serotonin 2A receptor antagonism, >100-fold selectivity over other serotonin subtype receptors, and high affinity for the α1 receptor. Moreover, upon local administration, this compound showed superior ocular hypotensive action in vivo relative to the clinically used reference compound timolol.
- Furlotti, Guido,Alisi, Maria Alessandra,Cazzolla, Nicola,Ceccacci, Francesca,Garrone, Beatrice,Gasperi, Tecla,La Bella, Angela,Leonelli, Francesca,Loreto, Maria Antonietta,Magarò, Gabriele,Mangano, Giorgina,Bettolo, Rinaldo Marini,Masini, Emanuela,Miceli, Martina,Migneco, Luisa Maria,Vitiello, Marco
-
supporting information
p. 1597 - 1607
(2018/07/30)
-
- HETEROARYL-SUBSTITUTED TRIAZOLES AS APJ RECEPTOR AGONISTS
-
Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.
- -
-
Paragraph 0756
(2018/06/12)
-
- Access to 1: H -indazoles, 1 H -benzoindazoles and 1 H -azaindazoles from (het)aryl azides: A one-pot Staudinger-aza-Wittig reaction leading to N-N bond formation?
-
The synthesis of various substituted 1H-indazoles is reported through N-N bond formation from an iminophosphorane derivative. Supported by control experiments, an original Staudinger-aza-Wittig tandem mechanism is proposed for this transformation.
- Alaime,Daniel,Hiebel,Pasquinet,Suzenet,Guillaumet
-
p. 8411 - 8414
(2018/08/06)
-
- Sulfocoumarin-, Coumarin-, 4-Sulfamoylphenyl-Bearing Indazole-3-carboxamide Hybrids: Synthesis and Selective Inhibition of Tumor-Associated Carbonic Anhydrase Isozymes IX and XII
-
A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 a–g (amide derivatives) and 7 a–h (triazoles) act as “prodrugs”, and their hydrolysis products are the de facto CA inhibitors. These compounds displayed sub-micromolar to high-nanomolar inhibitory activity against hCA isoforms IX and XII, which were recently validated as antitumor drug targets. Moreover, no inhibition of the off-target hCA I and II isoforms was observed. Compounds 8 a–f (another set of triazoles) exhibited nanomolar inhibition against hCA isoforms I, II, IX and XII, among which compounds 8 c, 8 d, and 8 f were found to inhibit the tumor-associated hypoxia-induced hCA isoform IX with Ki values of 1.8, 2.3, and 2.0 nm respectively. Further exploration of these compounds could be useful for the development of novel antitumor agents with selective mechanisms of CA inhibitory action.
- Angapelly, Srinivas,Sri Ramya,Angeli, Andrea,Supuran, Claudiu T.,Arifuddin, Mohammed
-
p. 1578 - 1584
(2017/10/16)
-
- Indazole-oxadiazole derivative, medicinal composition containing derivative, and application of derivative in tumor prevention
-
The invention discloses an indazole-oxadiazole derivative with the structure represented by general formula a shown in the description, or a pharmaceutically acceptable salt or solvate thereof. In the formula, X is O or N, Y is N, Z is N or O, and all groups are as defined in the description. The invention also discloses a medicinal composition adopting the derivative as an active component, and a use of the derivative. Compounds synthesized in the invention have an HIF-1 inhibition effect, and most of the compounds have a substantial HIF-1 inhibition effect, have strong in-vivo and in-vitro anti-HIF-1 effect on human colorectal carcinoma cell strains (HCT116) and other tumor cell strains, and can be used for treating tumor diseases.
- -
-
Paragraph 0136; 0137; 0138
(2017/07/25)
-
- Novel potent HIF-1 inhibitors for the prevention of tumor metastasis: discovery and optimization of 3-aryl-5-indazole-1,2,4-oxadiazole derivatives
-
Hypoxia inducible factor-1 (HIF-1) is the key transcription factor of cellular response to hypoxia and plays a critical role in tumor metastasis. We describe here the discovery and a structure-activity relationship study of a series of 3-aryl-5-indazole-1,2,4-oxadiazole derivatives as novel HIF-1 inhibitors. The two most promising compounds 4g and 4h inhibit HIF-1 transcription with IC50 values of 0.62 and 0.55 μM in vitro, respectively, and they exhibit more efficient HIF-1 inhibition in xenograft tumors than YC-1, a potential anticancer drug targeting HIF-1. In addition, they also remarkably prevent the hypoxia-driven migration of SKOV3 cells in vitro and tumor metastasis in vivo. Further investigation of the mechanism revealed that the two inhibitors could decrease HIF-1α and VEGF expression. These results suggest that our newly synthesized HIF-1 inhibitors 4g and 4h are potential therapeutic agents with which to treat tumor metastasis.
- Sheng, Rong,Li, Shan,Lin, Guanyu,Shangguan, Shihao,Gu, Yongchuan,Qiu, Ni,Cao, Ji,He, Qiaojun,Yang, Bo,Hu, Yongzhou
-
p. 81817 - 81830
(2015/10/12)
-
- IMMUNOASSAY FOR SYNTHETIC CANNABINOIDS OF THE 3-ADAMANTANYL INDAZOLE/INDOLE-3-CARBOXAMIDE FAMILY
-
An immunoassay method for detecting and determining adamantane substituted indazole and indole synthetic cannabinoids is described. Also described are components for use in implementing the method, namely, antibodies, detection agents, solid state devices and kits as well as immunogens used to raise the antibodies.
- -
-
Paragraph 0017
(2015/12/18)
-
- ALKYNYL ALCOHOLS AND METHODS OF USE
-
The invention relates to compounds of Formula (0): wherein Q, A1-A8, R4 and R5 and each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over- activation of NF-kB signaling is observed.
- -
-
Page/Page column 106; 107
(2015/03/13)
-
- HETEROARYL COMPOUNDS AS 5-HT4 RECEPTOR LIGANDS
-
The present invention relates to novel compounds of formula (I), and their pharmaceutically acceptable salts and compositions containing them. The present invention also relates to a process for the preparation of above said novel compounds, and their pharmaceutically acceptable salts. The compounds of formula (I) are useful in the treatment of various disorders that are related to 5-HT4 receptors.
- -
-
Paragraph 0122-0124
(2014/07/08)
-
- One-pot synthesis of novel 3,5-disubstituted-1,2,4-oxadiazoles from indazole carboxylic acid esters and amidoximes
-
An efficient and high-yielding one-pot synthesis of 3,5-disubstituted-1,2, 4-oxadiazoles from indazole carboxylic acid methyl esters and amidoximes is described. In this study a series of novel 3,5-disubstituted-1,2,4-oxadiazoles (3a-d), (4a-d), (5a-d), (6a-d), (7a-d) were synthesized using amidoximes 2a-d and indazole carboxylic acid esters (3-6).
- Swamy, Udutha Kumara,Mohan, H. Rama,Prasad, U. Viplava,Suresh,Kumar, T. Laxmi
-
p. 1921 - 1930
(2014/06/09)
-
- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
-
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
- -
-
Paragraph 00210; 00211
(2013/08/28)
-
- Optimization of N-benzoylindazole derivatives as inhibitors of human neutrophil elastase
-
Human neutrophil elastase (HNE) is an important therapeutic target for treatment of pulmonary diseases. Previously, we identified novel N-benzoylindazole derivatives as potent, competitive, and pseudoirreversible HNE inhibitors. Here, we report further development of these inhibitors with improved potency, protease selectivity, and stability compared to our previous leads. Introduction of a variety of substituents at position 5 of the indazole resulted in the potent inhibitor 20f (IC50 ~10 nM) and modifications at position 3 resulted the most potent compound in this series, the 3-CN derivative 5b (IC50 = 7 nM); both derivatives demonstrated good stability and specificity for HNE versus other serine proteases. Molecular docking of selected N-benzoylindazoles into the HNE binding domain suggested that inhibitory activity depended on geometry of the ligand-enzyme complexes. Indeed, the ability of a ligand to form a Michaelis complex and favorable conditions for proton transfer between Hys57, Asp102, and Ser195 both affected activity.
- Crocetti, Letizia,Schepetkin, Igor A.,Cilibrizzi, Agostino,Graziano, Alessia,Vergelli, Claudia,Giomi, Donatella,Khlebnikov, Andrei I.,Quinn, Mark T.,Giovannoni, Maria Paola
-
p. 6259 - 6272
(2013/09/02)
-
- COMPOUNDS AND THERAPEUTIC USES THEREOF
-
The invention relates to compounds, pharmaceutical compositions and methods useful for treating cancer, systemic or chronic inflammation, rheumatoid arthritis, diabetes, obesity, T-cell mediated autoimmune disease, ischemia, and complications associated w
- -
-
Page/Page column 68
(2013/02/28)
-
- INDAZOLE DERIVATIVES AS ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD) INHIBITORS FOR USE IN DIABETES AND RELATED DISEASES OF METABOLIC SYNDROME
-
Herein, we describe a method for treatment of diabetes and other disorders classified as Metabolic Syndrome. The invention provides novel AMP Deaminase (AMPD) inhibitors comprising novel indazole and benzotriazole derivatives including a phosphorous containing derivative, a carboxylic acid, or an amino acid ester prodrug. The invention also provides support for a novel mechanism of action for the existing drug metformin: direct inhibition of the enzyme AMPD. The inhibition of AMPD in turn activates AMP Kinase, known to be linked to the action of metformin. The invention also makes novel use of a double inhibitor assay allowing identification of selective AMPD inhibitors over ADA inhibitors. The new inhibitors, structurally distinct from metformin, offer selectivity that may obviate side effects known for metformin itself, providing new benefits for diabetes and Metabolic Syndrome.
- -
-
Page/Page column 3
(2012/06/01)
-
- LONIDAMINE ANALOGUES FOR FERTILITY MANAGEMENT
-
Fertility management can include: administering to the subject one or more doses of a compound according to Formula I so as to reduce fertility in the subject. Fertility management can also include administering an effective amount of the compound to: impair Sertoli cell function in a male subject; inhibit spermatogenesis in the subject; reduce testis weight in the subject; reduce ovary weight in a female subject; reduce serum progesterone in the female subject; impair ovarian follicle function in the female subject; causing reversible fertility in the subject. In order to return fertility, the method can include ceasing administration of the compound to the subject so as to return fertility in the subject. The compound can be administered for irreversibly sterilizing the subject.
- -
-
Page/Page column 69-70
(2011/02/24)
-
- Design, synthesis and evaluation of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase
-
Human neutrophil elastase (HNE) plays an important role in tumour invasion and inflammation. A series of N-benzoylindazoles was synthesized and evaluated for their ability to inhibit HNE. We found that this scaffold is appropriate for HNE inhibitors and that the benzoyl fragment at position 1 is essential for activity. The most active compounds inhibited HNE activity with IC50 values in the submicromolar range. Furthermore, docking studies indicated that the geometry of an inhibitor within the binding site and energetics of Michaelis complex formation were key factors influencing the inhibitor's biological activity. Thus, N-benzoylindazole derivatives and their analogs represent novel structural templates that can be utilized for further development of efficacious HNE inhibitors.
- Crocetti, Letizia,Giovannoni, Maria Paola,Schepetkin, Igor A.,Quinn, Mark T.,Khlebnikov, Andrei I.,Cilibrizzi, Agostino,Piaz, Vittorio Dal,Graziano, Alessia,Vergelli, Claudia
-
scheme or table
p. 4460 - 4472
(2011/09/12)
-
- Synthesis of 3-indazolecarboxylic esters and amides via Pd-catalyzed carbonylation of 3-iodoindazoles
-
A straightforward and effective procedure for the preparation of 1H-indazole-3-carboxylic acid esters and amides was developed. A series of functionalized 3-iodoindazoles were subjected to Pd-catalyzed carbonylations in the presence of methanol or amines,
- Buchstaller, Hans-Peter,Wilkinson, Kai,Burek, Kasimir,Nisar, Yasmin
-
experimental part
p. 3089 - 3098
(2011/10/13)
-
- Efficient two-step sequence for the synthesis of 2,5-disubstituted furan derivatives from functionalized nitroalkanes: Successive Amberlyst A21- and Amberlyst 15-catalyzed processes
-
The nitroaldol reaction of ketal-functionalized nitroalkanes with α-oxoaldehydes, promoted by Amberlyst A21, followed by acidic treatment (Amberlyst 15) of the obtained nitroalkanol, leads to the formation of 2,5-disubstituted furans in good yields. The p
- Palmieri, Alessandro,Gabrielli, Serena,Ballini, Roberto
-
supporting information; experimental part
p. 6165 - 6167
(2010/10/20)
-
- COMPOUNDS FOR TREATING MUSCULAR DYSTROPHY
-
Compounds of formula (I): wherein X, L1, R1, L2, R2, R3, and R4 are as defined herein, are useful in the treatment or prophylaxis of Duchenne muscular dystrophy, Becker muscular dystrophy, or cachexia.
- -
-
Page/Page column 43
(2010/12/29)
-
- Quantum mechanical study and vibrational spectra of indazolium-3- carboxylate and its decarboxylation product, the N-heterocyclic carbene indazol-3-ylidene
-
Indazolium-3-carboxylate is a molecule that can be found as the nucleus of several pseudo-cross-conjugated mesomeric betaines, such as the alkaloid nigellicine. From a chemical point of view, one of the more interesting properties of this class of molecules is the possibility of forming an N-heterocyclic carbene by thermal decarboxylation. In this paper we have studied the carbene generation by decarboxylation of 1,2-dimethyl indazolium-3- carboxylate, using vibrational (infrared and Raman) spectroscopy and quantum chemistry calculations. Normal mode analysis allowed us to analyse the changes in the stretching force constants upon decarboxylation and to establish spectroscopic-structure relationships. We also investigate the effect of 5-halogen (fluoro, chloro) substitution on the carbene generation. Decarboxylation energy profiles of the three derivatives were calculated. Crossing of the energy paths when going from the transition state to the final product were obtained. The theoretical tendency found for the activation energies agrees with that observed for the decarboxylation temperatures and for the calculated NICS values of the benzene moieties. the Owner Societies.
- Schmidt, Andreas,Snovydovych, Bohdan,Casado, Juan,Quirante, Jose Joaquin,Navarrete, Juan Teodomiro Lopez,Ramirez, Francisco Javier
-
scheme or table
p. 341 - 348
(2009/04/10)
-
- Novel Inhibitors of Hepatitis C Virus Replication
-
The embodiments provide compounds of the general Formula I, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
- -
-
Page/Page column 54-55
(2009/10/21)
-
- Synthesis of indazoles by the [3+2] cycloaddition of diazo compounds with arynes and subsequent acyl migration
-
(Chemical Equation Presented) The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions. Simple diazomethane derivatives afford N-unsubstituted indazoles or 1-arylated indazoles, depending upon the stoichiometry of the reagents and the reaction conditions, while dicarbonyl-containing diazo compounds undergo carbonyl migration to afford 1-acyl or 1-alkoxycarbonyl indazoles selectively.
- Liu, Zhijian,Shi, Feng,Martinez, Pablo D. G.,Raminelli, Cristiano,Larock, Richard C.
-
p. 219 - 226
(2008/09/17)
-
- New practical access to 2-azatryptophans and dehydro derivatives via the Wittig-Horner reaction
-
The Wittig-Horner reaction of protected 3-formylindazoles 1 with (±)-N-(benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester 2 has been developed as a new practical synthesis of dehydro 2-azatryptophans and amino acid derivatives. The preparation of 5-br
- Crestey, Fran?ois,Collot, Valérie,Stiebing, Silvia,Lohier, Jean-Fran?ois,Santos, Jana Sopkova-de Oliveira,Rault, Sylvain
-
p. 2457 - 2460
(2007/10/03)
-
- CONDENSED PYRAZOLE DERIVATIVES AS PPAR AGONISTS II
-
The invention discloses compounds of formula (I) wherein: R is a carboxylic acid or a derivative thereof; R1 and R2 are independently H or alkyl, or together R1 and R2 form an alkylene group; L1 is a
- -
-
Page/Page column 14
(2010/11/26)
-
- Synthesis and SAR of indazole-pyridine based protein kinase B/Akt inhibitors
-
A series of heteroaryl-pyridine containing inhibitors of Akt are reported. The synthesis and structure-activity relationships are discussed, leading to the discovery of a indazole-pyridine analogue (Ki = 0.16 nM). These compounds bind in the ATP binding site, are potent, ATP competitive, and reversible inhibitors of Akt activity. No selectivity amongst the Akt isoforms is observed for this analogue, but there is good selectivity against an panel of other kinases. It is least selective for other members of the AGC family of kinases but is nonetheless 40-fold selective for Akt over PKA. The compound shows cellular activity and significantly slows tumor growth in vivo.
- Woods, Keith W.,Fischer, John P.,Claiborne, Akiyo,Li, Tongmei,Thomas, Sheela A.,Zhu, Gui-Dong,Diebold, Robert B.,Liu, Xuesong,Shi, Yan,Klinghofer, Vered,Han, Edward K.,Guan, Ran,Magnone, Shayna R.,Johnson, Eric F.,Bouska, Jennifer J.,Olson, Amanda M.,Jong, Ron de,Oltersdorf, Tilman,Luo, Yan,Rosenberg, Saul H.,Giranda, Vincent L.,Li, Qun
-
p. 6832 - 6846
(2007/10/03)
-
- Indazole-carboxamide compounds
-
The invention provides novel indazole-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.
- -
-
Page/Page column 23
(2008/06/13)
-
- Crystalline form of an indazole-carboxamide compound
-
The invention provides crystalline halide salts of 1-isopropyl-1H-indazole-3-carboxylic acid {(1S,3R,5R)-8-[2-(4-acetylpiperazin-1-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}amide and solvates thereof. The invention also provides pharmaceutical compositions comprising such salts, methods of using such crystalline salts to treat diseases associated with 5-HT4 receptor activity, and processes useful for preparing such crystalline salts.
- -
-
Page/Page column 10
(2008/06/13)
-
- Lonidamine analogues and their use in male contraception and cancer treatment
-
Novel compounds useful for inhibiting spermatogenesis and cancer treatment, and in particular as inhibitors of heat shock proteins and/or elongation factor 1 alpha.
- -
-
Page/Page column 25
(2008/06/13)
-
- METHOD FOR SYNTHESIS OF LONIDAMINE AND RELATED INDAZOLE DERIVATIVES
-
Methods are provided for making highly pure preparations of lonidamine and related indazole derivatives.
- -
-
Page/Page column 18-20
(2008/06/13)
-
- Benzimidazole derivatives and their use as KDR kinase protein inhibitors
-
The invention discloses and claims benzimidazole compounds of formula (I): wherein X is C—R2; Y is C—R2 or C—R3; W and Z are each C—R3; R1 is an optionally substituted aryl, heteroaryl or a saturated 5- or 6-membered monocyclic heterocyclic radical or a b
- -
-
-
- INDAZOLE-CARBOXAMIDE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS
-
The invention provides novel indazole-carboxamide 5-HT4 receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds.
- -
-
Page/Page column 40-41
(2010/02/13)
-
- SUBSTITUTED THIAZOLE AND PYRIMIDINE DERIVATIVES AS MELANOCORTIN RECEPTOR MODULATORS
-
The present invention provides substituted thiazole and pyrimidine derivatives of Formula (I), methods of their preparation, pharmaceutical compositions comprising the compounds of Formula (I), and methods of use in treating human or animal disorders. The compounds of the invention can be useful as inhibitors of action of AgRP on a melanocortin receptor and thus can be useful for the management, treatment, control, or the adjunct treatment of diseases which may be responsive to the modulation of melanocortin receptors including obesity-related disorders.
- -
-
Page/Page column 134
(2010/02/14)
-
- VLA-4 INHIBITORS
-
The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
- -
-
-
- Blockade of voltage dependent sodium channels
-
Compounds of formula (1), and pharmaceutically acceptable salts thereof, are capable of blockading voltage-dependent sodium channels and are useful in particular, in treating glaucoma and multiple sclerosis.
- -
-
-
- Kinase inhibitors
-
Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
- -
-
-
- Practical synthesis of 1H-indazole-3-carboxylic acid and its derivatives
-
A practical and convenient synthesis of 1H-indazole-3-carboxylic acid and its amide and ester derivatives from the corresponding derivatives of 2-nitrophenylacetic acid was described.
- Yoshida, Toyokichi,Matsuura, Noriyasu,Yamamoto, Katsuhisa,Doi, Masahiro,Shimada, Kanji,Morie, Toshiya,Kato, Shiro
-
p. 2701 - 2712
(2007/10/03)
-