- INHIBITOR COMPOUNDS
-
The disclosure relates to heterocyclic compounds and methods for their preparation. The disclosure provides compounds that may have beneficial therapeutic activity in the treatment of a disease or condition mediated by excessive or otherwise undesirable Des1 and/or fibrotic activity.
- -
-
Page/Page column 63; 96-99
(2021/01/29)
-
- MITOCHONDRIAL TARGETING COMPOUNDS FOR THE TREATMENT OF ASSOCIATED DISEASES
-
Mitochondrial targeting compounds for the treatment of cancer and other disorders associated with mitochondrial function, including diabetes, autoimmune diseases, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases and their preparation. The present invention is also directed to the pharmaceutical compositions and treatment methods, prodrugs based on those compounds and the use thereof.
- -
-
Page/Page column 78
(2021/12/08)
-
- Promoting Effect of Crystal Water Leading to Catalyst-Free Synthesis of Heteroaryl Thioether from Heteroaryl Chloride, Sodium Thiosulfate Pentahydrate, and Alcohol
-
It is observed the crystal water in sodium thiosulfate pentahydrate (Na2S2O3·5H2O) can promote its multicomponent reaction with heteroaryl chlorides and alcohols, providing a facile, green, and specific synthesis of unsymmetrical heteroaryl thioethers via one-step formation of two C-S bonds under catalyst-, additive-, and solvent-free conditions. Mechanistic studies suggest that the crystal water in Na2S2O3·5H2O is crucial in generating the key thiol intermediates and byproduct NaHSO4, which then catalyzes the dehydrative substitution of alcohols with thiols to afford thioethers.
- Ma, Xiantao,Yu, Jing,Yan, Ran,Yan, Mengli,Xu, Qing
-
p. 11294 - 11300
(2019/09/12)
-
- HETEROARYL ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS
-
The present disclosure relates to compounds of formula I that are useful as modulators of 7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the centr
- -
-
Page/Page column 42
(2019/04/16)
-
- Efficient Generation of C–S Bonds via a By-Product-Promoted Selective Coupling of Alcohols, Organic Halides, and Thiourea
-
A metal- and base-free three-component coupling of alcohols, heteroaryl halides, and thiourea has been developed for direct and selective synthesis of heteroaryl thioethers. This method can be easily scaled up to the gram scale and extended to dialkyl thioethers, heteroaryl selenides, benzothiazoles, and some antimycobacterially-active thioethers. Mechanistic studies revealed that a by-product-promoted in situ C–O activation of alcohols to more reactive alkyl halides and slow release of the thiol and alkyl halide intermediates are the key to the high selectivity and success of the reaction. (Figure presented.).
- Ma, Xiantao,Yu, Lei,Su, Chenliang,Yang, Yaqi,Li, Huan,Xu, Qing
-
supporting information
p. 1649 - 1655
(2017/05/29)
-
- Selective IKur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide
-
We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further characterization in vivo, compound 1 demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2′ position for a series of close analogues by employing hydrogen bond donors. As a result, 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was identified as the lead compound in this series. Compound 25 showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clinical candidate. Further optimization of 25 to mitigate pH-dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile.
- Gunaga, Prashantha,Lloyd, John,Mummadi, Somanadham,Banerjee, Abhisek,Dhondi, Naveen Kumar,Hennan, James,Subray, Veena,Jayaram, Ramya,Rajugowda, Nagendra,Umamaheshwar Reddy, Kommuri,Kumaraguru, Duraimurugan,Mandal, Umasankar,Beldona, Dasthagiri,Adisechen, Ashok Kumar,Yadav, Navnath,Warrier, Jayakumar,Johnson, James A.,Sale, Harinath,Putlur, Siva Prasad,Saxena, Ajay,Chimalakonda, Anjaneya,Mandlekar, Sandhya,Conder, MaryLee,Xing, Dezhi,Gupta, Arun Kumar,Gupta, Anuradha,Rampulla, Richard,Mathur, Arvind,Levesque, Paul,Wexler, Ruth R.,Finlay, Heather J.
-
supporting information
p. 3795 - 3803
(2017/05/19)
-
- 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 00297
(2017/10/06)
-
- SULFONAMIDE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
-
Provided is a sulfonamide derivative represented by the following general formula (1) and having an α4 integrin inhibitory effect with high selectivity with a low effect on α4β1 and a high effect on α4β7, or a pharmaceutically acceptable salt thereof (in the general formula (1), A, B, D, E, R41, and a to h are as described in the description).
- -
-
Paragraph 0332; 0333
(2016/09/26)
-
- Boronic species as promising inhibitors of the Staphylococcus aureus NorA efflux pump: Study of 6-substituted pyridine-3-boronic acid derivatives
-
In response to the extensive use of antibiotics, bacteria have evolved numerous mechanisms of defense against antimicrobial agents. Among them, extrusion of the antimicrobial agents outside the bacterial cell through efflux pumps is a major cause of concern. At first limited to one or few structurally-related antibiotics, bacterial resistance have then progressed towards cross-resistance between different classes of antibiotics, leading to multidrug-resistant microorganisms. Emergence of these pathogens requires development of novel therapeutic strategies and inhibition of efflux pumps appears to be a promising strategy that could restore the potency of existing antibiotics. NorA is the most studied chromosomal efflux pump of Staphylococcus aureus; it is known to be implied in resistance of Methicillin-resistant S. aureus (MRSA) strains against a wide range of unrelated substrates, including hydrophilic fluoroquinolones. Starting from 6-benzyloxypyridine-3-boronic acid I that we previously identified as a potential inhibitor of the NorA efflux pump against the NorA-overexpressing S. aureus 1199B strain (SA1199B), we describe here the synthesis and biological evaluation of a series of 6-(aryl)alkoxypyridine-3-boronic acids. 6-(3-Phenylpropoxy)pyridine-3-boronic acid 3i and 6-(4-phenylbutoxy)pyridine-3-boronic acid 3j were found to potentiate ciprofloxacin activity by a 4-fold increase compared to the parent compound I. In addition, it has been shown that both compounds promote Ethidium Bromide (EtBr) accumulation in SA1199B, thus corroborating their potential mode of action as NorA inhibitors.
- Fontaine, Fanny,Héquet, Arnaud,Voisin-Chiret, Anne-Sophie,Bouillon, Alexandre,Lesnard, Aurélien,Cresteil, Thierry,Jolivalt, Claude,Rault, Sylvain
-
p. 185 - 198
(2015/04/14)
-
- SULFONAMIDE DERIVATIVE AND MEDICINAL USE THEREOF
-
Provided are sulfonamide derivatives of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action.
- -
-
Paragraph 0182; 0794
(2015/02/25)
-
- SULFONAMIDE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG
-
The present invention relates to Sulfonamide Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, W, X, R1, R2, R3, R4 and R5 are as defined herein. The present invention also relates to compositions comprising at least one Sulfonamide Derivative, and methods of using the Sulfonamide Derivatives for improving the pharmacokinetics of a drug.
- -
-
Paragraph 0262
(2015/07/22)
-
- 2-phenylindole and arylsulphonamide: Novel scaffolds bactericidal against mycobacterium tuberculosis
-
A cellular activity-based screen on Mycobacterium tuberculosis (Mtb) H37Rv using a focused library from the AstraZeneca corporate collection led to the identification of 2-phenylindoles and arylsulphonamides, novel antimycobacterial scaffolds. Both the series were bactericidal in vitro and in an intracellular macrophage infection model, active against drug sensitive and drug resistant Mtb clinical isolates, and specific to mycobacteria. The scaffolds showed promising structure-activity relationships; compounds with submicromolar cellular potency were identified during the hit to lead exploration. Furthermore, compounds from both scaffolds were tested for inhibition of known target enzymes or pathways of antimycobacterial drugs including InhA, RNA polymerase, DprE1, topoisomerases, protein synthesis, and oxidative-phosphorylation. Compounds did not inhibit any of the targets suggesting the potential of a possible novel mode of action(s). Hence, both scaffolds provide the opportunity to be developed further as leads and tool compounds to uncover novel mechanisms for tuberculosis drug discovery.
- Naik, Maruti,Ghorpade, Sandeep,Jena, Lalit Kumar,Gorai, Gopinath,Narayan, Ashwini,Guptha, Supreeth,Sharma, Sreevalli,Dinesh, Neela,Kaur, Parvinder,Nandishaiah, Radha,Bhat, Jyothi,Balakrishnan, Gayathri,Humnabadkar, Vaishali,Ramachandran, Vasanthi,Naviri, Lava Kumar,Khadtare, Pallavi,Panda, Manoranjan,Iyer, Pravin S.,Chatterji, Monalisa
-
supporting information
p. 1005 - 1009
(2014/12/10)
-
- ANTIVIRAL COMPOUNDS
-
The present invention discloses compounds of Formula (I): wherein the variables in Formula (I) are defined as described herein. Also disclosed are pharmaceutical compositions containing such compounds and methods for using the compounds of Formula (I) in the prevention or treatment of HCV infection.
- -
-
Page/Page column 86
(2014/09/29)
-
- SULFONAMIDE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG
-
The present invention relates to Sulfonamide Derivatives of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, W, X, R1, R2, R3, R4 and R5 are as defined herein. The present invention also relates to compositions comprising at least one Sulfonamide Derivative, and methods of using the Sulfonamide Derivatives for improving the pharmacokinetics of a drug.
- -
-
Page/Page column 58
(2014/01/17)
-
- SULFONAMIDE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG
-
The present invention relates to Sulfonamide Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, W, X, R1, R2, R3, R4 and R5 are as defined herein. The present invention also relates to compositions comprising at least one Sulfonamide Derivative, and methods of using the Sulfonamide Derivatives for improving the pharmacokinetics of a drug.
- -
-
Page/Page column 58
(2014/01/17)
-
- SULFONAMIDE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG
-
The present invention relates to Sulfonamide Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, W, X, R1, R2, R3, R4 and R5 are as defined herein. The present invention also relates to compositions comprising at least one Sulfonamide Derivative, and methods of using the Sulfonamide Derivatives for improving the pharmacokinetics of a drug.
- -
-
Paragraph 0261; 0262
(2014/02/15)
-
- NEW COMPOUNDS 384
-
The present invention relates to a compound of formula (I) as a free base or a pharmaceutically acceptable salt thereof. The present invention also relates to pharmaceutical formulations containing said compound and to the use of said compound in therapy.
- -
-
Page/Page column 71
(2008/06/13)
-
- INHIBITORS OF 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE 1
-
The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salts or solvates thereof, wherein n, X, Y, R1, R2, R3 and R4 are as described in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating conditions that are mediated by the modulation of 11 βHSD1 , the method comprising administering to a mammal an effective amount of a compound of formula (I).
- -
-
Page/Page column 24
(2010/11/25)
-
- PIPERAZINE DERIVATIVES USEFUL FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS
-
The invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Ra, Rb, Rc, Rd, Re, Rf and Y are as defined in the specification. The compounds are partial or full agonists at the growth hormone secretagogue (GHS) receptors . Pharmaceutical compositions comprising the compounds, methods of preparing the compounds, uses of the compounds and methods involving the compounds are also provided.
- -
-
Page/Page column 55
(2010/02/15)
-