- DEGRADATION OF BRUTON'S TYROSINE KINASE (BTK) BY CONJUGATION OF BTK INIDBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE
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Disclosed herein are novel bifunctional compounds formed by conjugating BTK inhibitor moieties with E3 ligase Ligand moieties, which function to recruit targeted proteins to E3 ubiquitin ligase for degradation, and methods of preparation and uses thereof.
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Paragraph 0404; 0405
(2021/02/05)
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- LIQUID CRYSTAL COMPOUND, LIQUID CRYSTAL COMPOSITION AND LIQUID CRYSTAL DISPLAY ELEMENT
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PROBLEM TO BE SOLVED: To improve Δn of a liquid crystal compound. SOLUTION: One aspect of the present invention is a liquid crystal compound represented by general formula (i) [where Ri1 is a C1 to 15 alkyl group or the like, Ri2 is
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Paragraph 0169-0170
(2020/02/28)
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- Bcl-2 INHIBITORS
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Disclosed herein is a compound of Formula (I) for inhibiting Bcl-2 and treating disease associated with undesirable bcl-2 activity (Bcl-2 related diseases), a method of using the compounds disclosed herein for treating dysregulated apoptotic diseases including cancers and treating autoimmune disease, and a pharmaceutical composition comprising the same.
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Paragraph 1125
(2019/11/19)
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- Photochemical Homologation for the Preparation of Aliphatic Aldehydes in Flow
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Cheap and readily available aqueous formaldehyde was used as a formylating reagent in a homologation reaction with nonstabilized diazo compounds, enabled by UV photolysis of bench-stable oxadiazolines in a flow photoreactor. Various aliphatic aldehydes were synthesized along with the corresponding derivatized alcohols and benzimidazoles. No transition-metal catalyst or additive was required to affect the reaction, which proceeded at room temperature in 80 min.
- Chen, Yiding,Leonardi, Marco,Dingwall, Paul,Labes, Ricardo,Pasau, Patrick,Blakemore, David C.,Ley, Steven V.
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p. 15558 - 15568
(2019/01/04)
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- PYRIDINE-1-OXIDE DERIVATIVES AND THEIR USE AS FACTOR XIA INHIBITORS
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The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.
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- Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy
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We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4′,4′-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.
- Tseng, Chih-Chung,Noordali, Hannah,Sani, Monica,Madhani, Melanie,Grant, Denis M.,Frenneaux, Michael P.,Zanda, Matteo,Greig, Iain R.
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p. 2780 - 2789
(2017/04/21)
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- FLUORO-PERHEXILINE COMPOUNDS AND THEIR THERAPEUTIC USE
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The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain fluoro-perhexiline compounds of the following formula (also referred to herein as FPER compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, for example, those which are known to be treated with, or known to be treatable with, perhexiline, including, for example, disorders that are ameliorated by the inhibition of carnitine palmitoyltransferase (CPT); cardiovascular disorders such as: angina pectoris; heart failure (HF); ischaemic heart disease (IHD); cardiomyopathy; cardiac dysrhythmia; stenosis of a heart valve; hypertrophic cardiomyopathy (HCM); coronary heart disease; and other disorders, for example, diabetes and cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.
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- BICYCLIC HETEROARYL DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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Bicyclic heteroaryl derivatives of Formula 1, and pharmaceutically acceptable salts, isomers, hydrates and solvates thereof can selectively and effectively inhibit DGAT1, and thus can be useful as medicines for effectively treating dangerous diseases such as obesity, type 2 diabetes, abnormal lipidemia, metabolic syndrome (syndrome X) and the like, which are caused by DGAT1, with no adverse side effects.
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Page/Page column 25
(2013/11/05)
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- BENZIMIDAZOLE DERIVATIVES USEFUL AS TRP M8 RECEPTOR MODULATORS
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The present invention is directed to benzimidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8 (transient receptor potential M8 channel). More particularly, the compounds of the present invention are useful in the treatment of inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold, anxiety and depression.
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Page/Page column 54-55
(2010/12/17)
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- SUBSTITUTED IMIDAZOLINE COMPOUNDS
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Substituted imidazoline derivatives corresponding to Formula I: a method for producing them from substituted aldehyde compounds of Formula B: and the use of such imidazoline derivatives and aldehyde compounds to treat pain, depression, urinary incontinenc
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Page/Page column 14; 16
(2009/03/07)
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- SPIROCYCLIC CYCLOHEXANE COMPOUNDS WITH ANALGESIC ACTIVITY
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Spirocyclic cyclohexane compounds corresponding to formula I a process for manufacturing such compounds, pharmaceutical compositions that contain such compounds, and the use of such spirocyclic cyclohexane compounds for the production of pharmaceuticals,
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Page/Page column 8
(2009/05/28)
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- Substituted Oxazole Compounds with Analgesic Activity
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Substituted oxazole derivatives corresponding to formula 1: a method for producing such compounds, pharmaceutical compositions containing such compounds, and the use of such compounds to treat pain, depression, urinary incontinence, diarrhoea, pruritus, a
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Page/Page column 13
(2009/04/24)
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- Substituted Cyclohexylmethyl Compounds
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Novel cyclohexylmethyl compounds corresponding to formula I wherein R1, R2, R3, R4 and R5, have the meanings given in the description. Pharmaceutical formulations containing these compounds, as well as a processes for preparing these compounds and related methods of treatment are also provided.
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Page/Page column 27
(2009/12/05)
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- Substituted Sulfonamide Compounds
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Substituted sulfonamide compounds corresponding to the formula I: processes for the preparation thereof, pharmaceutical composition containing these compounds and the use of substituted sulfonamide compounds for the preparation of pharmaceutical compositions.
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Page/Page column 86
(2009/10/17)
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- SUBSTITUTED OXADIAZOLE COMPOUNDS AND THEIR USE AS OPIOID RECEPTOR LIGANDS
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Substituted oxadiazole compounds corresponding to formula I: in which X denotes CH, CH2, CH═CH, CH2CH2, CH2CH═CH or CH2CH2CH2; R1 denotes aryl or heteroaryl, in each c
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Page/Page column 12
(2009/01/24)
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- Substituted Amide Compounds
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Substituted amide compounds corresponding to formula I: processes for preparing them, pharmaceutical compositions containing these compounds, and the use of substituted amide derivatives for the preparation of medicaments for the treatment of pain and various other conditions.
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Page/Page column 33; 35; 44-45
(2009/01/20)
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- Substituted Sulfonamide Compounds
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Substituted sulfonamide compounds corresponding to formula I pharmaceutical compositions comprising them, a process for preparing them, and the use of such compounds to treat or inhibit pain and other disorders or disease states.
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Page/Page column 17-18
(2009/01/24)
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- ARYLPROPIONAMIDE, ARYLACRYLAMIDE, ARYLPROPYNAMIDE, OR ARYLMETHYLUREA ANALOGS AS FACTOR XIA INHIBITORS
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The present invention provides compounds of Formula (I): Formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L1, M and R11 are as defined herein. The compounds of Formula (I) are selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
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Page/Page column 208
(2008/06/13)
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- 3-AMINO-PYRAZOLO[3,4B]PYRIDINES USED AS INHIBITORS OF PROTEIN TYROSINE KINASES FOR TREATING ANGIOGENIC, HYPERPROLIFERATIVE OR NEURODEGENERATIVE DISEASES
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The invention relates to compounds of general formula (I), in which R1 and R2 are described in the application, to the use of the compounds of general formula (I) as inhibitors of protein tyrosine kinases for treating various diseases, and to the compounds of general formulas (II) and (III) as intermediate compounds for producing compounds of general formula (I), in which X, R1a and R2a have the meanings as described in general formulas (II) and (III).
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Page/Page column 49
(2008/06/13)
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- New high affinity H3 receptor agonists without a basic side chain
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In this study, we replaced the basic amine function of the known histamine H3 receptor agonists imbutamine or immepip with non-basic alcohol or hydrocarbon moieties. All compounds in this study show a moderate to high affinity for the cloned human H3 receptor and, unexpectedly, almost all of them act as potent agonists. Moreover, in the alcohol series, we consistently observed an increased selectivity for the human H3 receptor over the human H4 receptor, but none of the compounds in this series possess increased affinity and functional activity compared to their alkylamine congeners. In this new series of compounds VUF5657, 5-(1H-imidazol-4-yl)-pentan-1-ol, is the most potent histamine H3 receptor agonist (pKi = 8.0 and pEC50 = 8.1) with a 320-fold selectivity at the human H3 receptor over the human H 4 receptor.
- Kitbunnadaj, Ruengwit,Hoffmann, Marcel,Fratantoni, Silvina A.,Bongers, Gerold,Bakker, Remko A.,Wieland, Kerstin,El Jilali, Ahmed,De Esch, Iwan J. P.,Menge, Wiro M. P. B.,Timmerman, Henk,Leurs, Rob
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p. 6309 - 6323
(2007/10/03)
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- Six-membered nitrogen ring formation by radical cyclization of trichloroacetamides with enones. A synthetic entry to cis-perhydroisoquinoline- 3,6-diones
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Intramolecular reactions between 1-(carbamoyl)dichloromethyl radicals and enones acting as radical acceptors are reported for the first time. The Bu 3SnH promoted 6-exo reaction of trichloroacetamides with enones, avoiding the 1,5-hydrogen transfer, constitutes a new synthetic entry to cis-perhydoisoquinoline-3,6-diones.
- Vila, Xavier,Quirante, Josefina,Paloma, Laura,Bonjoch, Josep
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p. 4661 - 4664
(2007/10/03)
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- Liquid-crystalline compound having dienyl moiety and liquid-crystal composition
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The present invention is concerned with a liquid crystalline compound expressed by general formula (1) STR1 wherein R1 represents cyano group, halogen atom, or a straight or branched alkyl group or halogenated alkyl group having 1 to 20 carbon
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- A synthesis of (±)-stemodinone: An application of organoiron chemistry to the construction of sterically congested quaternary carbon centers
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A synthesis of racemic stemodinone is described, using tricarbonyl(1-5- η-4-methoxy-1,3-dimethylcyclohexadienyl)iron(I) hexafluorophosphate (9) as an electrophile that is the A-ring precursor. Reaction of 9 with the tin enolate from 4,4-(ethylenedioxy)cyclohexanecarbaldehyde proceeded with excellent regioselectivity and high yield to generate an intermediate representing the A and C rings of the target molecule. The B ring was constructed by introducing a two-carbon electrophilic group onto the A ring, followed by ring closure using an intramolecular enolate alkylation. Installation of the D ring and manipulation to give the final product followed transformations precedented with this series of compounds.
- Pearson, Anthony J.,Fang, Xinqin
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p. 5284 - 5292
(2007/10/03)
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- Dialkyl-substituted dithianes and pesticidal compositions
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The present invention provides compounds of the formula (I): STR1 wherein m and n are independently selected from 0, 1 or 2, STR2 R is selected from hydrogen, methyl or ethyl; R1 is selected from C1-4 hydrocarbyl substituted by one to five halo atoms, and a group --C C--R9 wherein R9 is a group S(O)w --R10 wherein R10 is trifluoromethyl, methyl or ethyl and w is 0, 1 or 2 or R9 is a C3-5 aliphatic group or an aliphatic group containing up to 5 carbon atoms atoms substituted by C1-4 alkoxy, C2-6 alkoxyalkoxy, C1-8 acyloxy, halo or hydroxy, a group COR11 wherein R11 is hydrogen, C1-4 alkyl, C1-4 alkoxy or a group NR12 R13 wherein R12 and R13 are independently selected from hydrogen, methyl or ethyl, or R9 is SiR14 R15 R16 wherein R14 to R16 are the same or different and each is a C1-4 aliphatic group or R14 and R15 are C1-4 aliphatic groups and R16 is a phenyl group; R2, R3, R7 and R8 are independently selected from hydrogen, methyl or halo; R4a and R4b, R6a and R6b are independently selected from hydrogen, C1-3 alkyl, C2-3 alkenyl or alkynyl each being optionally substituted by halo, cyano or C1-4 alkoxy; cyano, halo or a group COR 11a wherein R11a is hydrogen, C1-4 alkoxy, C1-4 alkyl or a group NR12a R13a wherein R12a and R13a are independently selected from hydrogen, methyl or ethyl; R5a is a non-aromatic hydrocarbyl group containing up to seven carbon atoms, or phenyl each optionally substituted by cyano, halo, C1-4 alkyl, C1-4 haloalkyl, C3-4 cycloalkyl, C1-4 alkoxy or a group S(O)q R17 wherein q is 0, 1 or 2 and R17 is methyl or ethyl and R5b is hydrogen, hydroxy or C1-4 alkyl optionally substituted by alkoxy; and represents --CH--CH-- or --C=C-- which are useful pesticides, processes for their preparation, pesticidal formulations containing them and their use in the control or prevention of pest infestation.
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- (6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydrofolate and (6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydropteroyl-L-ornithine as Potential Antifolates and Antitumor Agents
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(6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydropteroic acid was synthesized in several steps from 4,4-(ethylenedioxy)cyclohexanone and triphenylphosphonium bromide and was elaborated to (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydr
- Rosowsky, Andre,Forsch, Ronald A.,Moran, Richard G.
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p. 709 - 715
(2007/10/02)
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- A Photochemical Approach to the Taxanes
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The de Mayo sequence has been applied to the inter- and intramolecular photocycloaddition of various cycloalkenes with homocamphorquinone derivatives to generate a model for the A, B, and C rings of the taxanes.A model sequence of reactions applicable to
- Berkowitz, W. F.,Amarasekara, A. S.,Perumattam, J. J.
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p. 1119 - 1124
(2007/10/02)
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- FURTHER EXTENSIONS OF THE KINETIC ENOLATE METHOD FOR TERPENOID SYNTHESES
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New stereorandom syntheses of juvabione and dehydrojuvabione using kinetic enolates as synthons are described.
- Ferrino, S. A.,Maldonado, L. A.
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p. 925 - 932
(2007/10/02)
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