cas 185122-74-1, 1H-INDEN-1-AMINE, 5-BROMO-2,3-DIHYDRO-

Articles about 185122-74-1Total 22 be found

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Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy
Hypercontractility of the cardiac sarcomere may be essential for the underlying pathological hypertrophy and fibrosis in genetic hypertrophic cardiomyopathies. Aficamten (CK-274) is a novel cardiac myosin inhibitor that was discovered from the optimization of indoline compound 1. The important advancement of the optimization was discovery of an Indane analogue (12) with a less restrictive structure-activity relationship that allowed for the rapid improvement of drug-like properties. Aficamten was designed to provide a predicted human half-life (t1/2) appropriate for once a day (qd) dosing, to reach steady state within two weeks, to have no substantial cytochrome P450 induction or inhibition, and to have a wide therapeutic window in vivo with a clear pharmacokinetic/pharmacodynamic relationship. In a phase I clinical trial, aficamten demonstrated a human t1/2 similar to predictions and was able to reach steady state concentration within the desired two-week window.
Ashcraft, Luke,Chin, Eva R.,Chuang, Chihyuan,Collibee, Scott,Cremin, Peadar,Hartman, James,Hwee, Darren T.,Malik, Fady I.,Morgan, Bradley P.,Robertson, Laura A.,Schaletzky, Julia,Vander Wal, Mark,Wang, Jingying,Wang, Wenyue,Wang, Xiaolin,Wehri, Eddie,Wu, Yangsong,Zamora, Jeanelle
supporting information
p. 14142 - 14152
(2021/10/20)

First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate
Inhibition of neuronal nitric oxide synthase (nNOS), an enzyme implicated in neurodegenerative disorders, is an attractive strategy for treating or preventing these diseases. We previously developed several classes of 2-aminoquinoline-based nNOS inhibitor
Cinelli, Maris A.,Reidl, Cory T.,Li, Huiying,Chreifi, Georges,Poulos, Thomas L.,Silverman, Richard B.
supporting information
p. 4528 - 4554
(2020/05/05)

Deconstructive Oxygenation of Unstrained Cycloalkanamines
A deconstructive oxygenation of unstrained primary cycloalkanamines has been developed for the first time using an auto-oxidative aromatization promoted C(sp3)?C(sp3) bond cleavage strategy. This metal-free method involves the substitution reaction of cycloalkanamines with hydrazonyl chlorides and subsequent auto-oxidative annulation to in situ generate pre-aromatics, followed by N-radical-promoted ring-opening and further oxygenation by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and m-cholorperoxybenzoic acid (mCPBA). Consequently, a series of 1,2,4-triazole-containing acyclic carbonyl compounds were efficiently produced. This protocol features a one-pot operation, mild reaction conditions, high regioselectivity and ring-opening efficiency, broad substrate scope, and is compatible with alkaloids, osamines, and peptides, as well as steroids.
Han, Bing,He, Yi-Heng,Pan, Jia-Hao,Wang, Yuan-Rui,Yu, Wei,Zhang, Jian-Wu
p. 3900 - 3904
(2020/02/11)

PERIPHERAL ALKYL AND ALKENYL CHAINS EXTENDED BENZENE DERIVATIVES AND PHARMACEUTICAL COMPOSITION INCLUDING THE SAME
The compounds represented by Formula (I), which are peripheral alkyl and alkenyl chains extended benzene derivatives, are useful as dual autotaxin (ATX) / histone deacetylase (HD AC) inhibitors. These compounds may be included in a pharmaceutical composition along with a pharmaceutically acceptable carrier, and be used in a therapeutically effective amount for prophylaxis or treatment of various diseases and disorders.
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(2020/10/20)

DIHYDROBENZOFURAN AND INDEN ANALOGS AS CARDIAC SARCOMERE INHIBITORS
Provided are compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein A, Z, B, R1, R2, R3, G1, G2, and G3 are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof Also provided are methods of using a compound of Formula (I), or a pharmaceutically acceptable salt, thereof for use in methods of treatment heart diseases through cardiac sarcomere inhibtion.
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Paragraph 0243

(2019/08/08)

Substituent effects on chiral resolutions of derivatized 1-phenylalkylamines by heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin GC stationary phase
Chiral resolutions of trifluoroacetyl-derivatized 1-phenylalkylamines with different type and position of substituent were investigated by capillary gas chromatography by using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin diluted in OV-1701 as a chiral stationary phase. The influence of column temperature on retention and enantioselectivity was examined. All enantiomers of meta-substituted analytes as well as fluoro-substituted analytes could be resolved. Temperature had a favorable influence on enantioselectivity for small amines with substituents at the ortho-position. The type of substituent at the stereogenic center of amines also had a crucial effect as the ethyl group led to poor enantioseparation. Among all analytes studied, trifluoroacetyl-derivatized 1-(2′-fluorophenyl)ethylamine exhibited baseline resolution with the shortest analysis time.
Issaraseriruk, Natthapol,Sritana-anant, Yongsak,Shitangkoon, Aroonsiri
supporting information
p. 900 - 906
(2018/05/08)

ISOQUINOLINE COMPOUNDS, A PROCESS FOR THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
A compound of formula (I): wherein the substituents are as defined in the description. Medicinal products containing the same which are useful in treating or preventing pathologies which are the result of activation of the RhoA/ROCK pathway and phosphorylation of the myosin light chain.
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(2017/06/12)

Substituted ring compound and its method and use thereof
The invention provides a substituted cyclic compound as well as a use method and application thereof. The compound is a compound as shown in a formula (I) or stereoisomers, stereomers, tautomers, nitric oxides, solvates, metabolites and pharmaceutically acceptable salts or prodrugs of the compound as shown in the formula (I). The invention further provides a medicament composition containing the compound. The compound and the medicament composition are capable of regulating the activity of protein kinase in a biological sample body and are used for protecting, treating or relieving proliferative diseases of patients. The formula (I) is as shown in the specification.
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(2017/08/25)

SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE
The present invention provides novel substituted alkynyl compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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(2014/06/24)

Structure based evolution of a novel series of positive modulators of the AMPA receptor
Starting from compound 1, we utilized biostructural data to successfully evolve an existing series into a new chemotype with a promising overall profile, exemplified by 19.
Jamieson, Craig,MacLean, John K.F.,Brown, Christopher I.,Campbell, Robert A.,Gillen, Kevin J.,Gillespie, Jonathan,Kazemier, Bert,Kiczun, Michael,Lamont, Yvonne,Lyons, Amanda J.,Moir, Elizabeth M.,Morrow, John A.,Pantling, John,Rankovic, Zoran,Smith, Lynn
scheme or table
p. 805 - 811
(2011/02/27)

INDANE DERIVATIVES
The present invention relates to anindane derivative according to formula I wherein the variables are defined as in the specification, or to a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to a pharmaceutical composition comprising one or more of said indane derivatives and to their use in therapy, for instance in the treatment or prevention of psychiatric diseases where an enhancement of synaptic responses mediated by AMPA receptors is required, including schizophrenia, depression and Alzheimer' s disease.
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Page/Page column 32

(2010/11/03)

INDANE DERIVATIVES AS AMPA RECEPTOR MODULATORS
The present invention relates to a heterocyclic derivative according to formula (I); wherein the variables are defined as in the specification, or to a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to a pharmaceut
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(2009/12/28)

ANTI-INFECTIVE PYRIMIDINES AND USES THEREOF
This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 187

(2009/04/25)

METALLOPROTEASE INHIBITORS
The present invention relates to amide containing aromatic MMP inhibiting compounds with a mono-amide heteroaromatic group, of formulas I and II:
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Page/Page column 62

(2008/06/13)

HETEROBICYCLIC METALLOPROTEASE INHIBITORS
The present invention relates generally to heterobicyclic containing pharmaceutical agents, and in particular, to heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic metalloprotease inhibiting compounds that exhibit an increased potency in relation to currently known metalloprotease inhibitors.
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Page/Page column 112, 125

(2008/12/05)

SUBSTITUTED FLUOROETHYL UREAS AS ALPHA 2 ADRENERGIC AGENTS
Therapeutic compounds, and methods, compositions, and medicaments related thereto are disclosed herein.
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Page/Page column 18

(2008/12/04)

Discovery and structure-activity relationship studies of indole derivatives as liver X receptor (LXR) agonists
A structurally novel liver X receptor (LXR) agonist (1) was identified from internal compound collection utilizing the combination of structure-based virtual screening and high-throughput gene profiling. Compound 1 increased ABCA1 gene expression by eightfold and SREBP1c by threefold in differentiated THP-1 macrophage cell lines. Confirmation of its agonistic activity against LXR was obtained in the co-factor recruitment and reporter transactivation assays. Structure-activity relationship studies on compound 1 are described.
Bakir, Farid,Kher, Sunil,Pannala, Madhavi,Wilson, Norma,Nguyen, Trang,Sircar, Ila,Takedomi, Kei,Fukushima, Chiaki,Zapf, James,Xu, Kui,Zhang, Shao-Hui,Liu, Juping,Morera, Lisa,Schneider, Lisa,Sakurai, Naoki,Jack, Rick,Cheng, Jie-Fei
p. 3473 - 3479
(2008/09/19)

HETEROBICYCLIC METALLOPROTEASE INHIBITORS
The present invention relates generally to amide group containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic MMP- 13 inhibiting compounds, that exhibit an increased potency in relation to currently known MMP- 13 inhibitors.
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Page/Page column 148-149

(2008/06/13)

Multicyclic bis-amide MMP inhibitors
The present invention relates generally to bis-amide group containing pharmaceutical agents, and in particular, to multicyclic bis-amide MMP-13 inhibitor compounds. More particularly, the present invention provides a new class of MMP-13 inhibiting compounds, containing a pyrimidinyl bis-amide group in combination with a heterocyclic moiety, that exhibit an increased potency and solubility in relation to currently known bis-amide group containing MMP-13 inhibitors.
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Page/Page column 50-51; 115

(2008/06/13)

NOVEL 2-AMINO BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF SMALL-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS
This invention relates to novel 2-amino benzimidazole derivatives useful as modulators of small-conductance calcium-activated potassium channels (SK channels). In other aspects the invention relates to the use of these compounds in a method for therapy an
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Page/Page column 20

(2008/06/13)

Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence, or bladder overactivity.
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Page 15

(2008/06/13)

CANNABINOID RECEPTOR LIGANDS
A compound of the formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein:R1, R2, L1, L2, M1, M2, n, p, q, A, D, X, Y and Z are as described in the specification; phar
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Page 38

(2008/06/13)