- THERAPEUTIC COMPOSITION OF CURE-PRO COMPOUNDS FOR TARGETED DEGRADATION OF BET DOMAIN PROTEINS, AND METHODS OF MAKING AND USAGE
-
The present application is directed to a therapeutic composition, comprising two precursor compounds (monomers) that are suitable for assembly via two or more reversible covalent bonds. The monomers are polyfunctionalized molecules comprising a bioorthogo
- -
-
Paragraph 0339; 0409
(2022/02/15)
-
- THERAPEUTIC CURE-PRO COMPOUNDS FOR TARGETED DEGRADATION OF BET DOMAIN PROTEINS, AND METHODS OF MAKING AND USING THEM
-
The present application is directed to a therapeutically useful compound, comprised of two monomers that are linked to each other through two or more reversible covalent bonds. Each monomer is a polyfunctionalized molecule comprising a bioorthogonal linker element and ligand or pharmacophore, wherein the linker and ligand/pharmacophore are covalently coupled to each other either directly or through an optional connector moiety.
- -
-
Paragraph 0325; 0394-0395
(2022/02/15)
-
- PROTEIN TAG TO INDUCE LIGAND DEPENDENT DEGRADATION OF PROTEIN/PROTEIN-FUSIONS
-
Disclosed is a dTAG system comprising small molecule degraders of mutant BET family protein-tagged proteins via recruitment of an E3 ubiquitin ligase and uses thereof.
- -
-
Paragraph 0197; 0204-0205
(2022/01/04)
-
- METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
-
The present disclosure relates to compounds and methods for modulating the expression of dmpk, and treating diseases and conditions in which dmpk plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
- -
-
Paragraph 00616; 00618; 00619; 00620
(2021/08/13)
-
- Recyclable palladium-catalyzed carbonylative annulation of 2-iodoanilines with acid anhydrides: A practical synthesis of 2-alkylbenzoxazinones
-
A highly efficient heterogeneous palladium-catalyzed carbonylative annulation of 2-iodoanilines and acid anhydrides has been developed. The reaction proceeds effectively in toluene using N,N-diisopropylethylamine (DiPEA) as the base at 100 °C under 2 bar of CO and provides a novel, general, and practical method for the assembly of a wide variety of 2-alkylbenzoxazinones with high functional group tolerance and good to excellent yields. This supported palladium complex can be readily separated from the product and recovered by a simple filtration of the reaction solution and reused up to seven times with almost consistent catalytic efficiency.
- Zhou, Zebiao,Huang, Bin,Cai, Mingzhong
-
p. 3150 - 3163
(2021/08/30)
-
- BENZIMIDAZOLES DERIVATIVES AS ANTI-TUBERCULOSIS AGENTS
-
The present invention provides novel compounds of benzimidazole derivatives as anti-tubercular agents and their pharmaceutically acceptable salts for use as bactericidal therapeutics. The invention also provides a pharmaceutical composition comprising a c
- -
-
Page/Page column 11
(2020/10/09)
-
- Evaluation of linker length effects on a BET bromodomain probe
-
Fueled by the therapeutic potential of the epigenetic machinery, BET bromodomains have seen high interest as drug targets. Herein, we introduce different linkers to a BET bromodomain benzodiazepine ligand (I-BET762) to gauge its implications in the develo
- Traquete, Rui,Henderson, Elizabeth,Picaud, Sarah,Cal, Pedro M. S. D.,Sieglitz, Florian,Rodrigues, Tiago,Oliveira, Rudi,Filippakopoulos, Panagis,Bernardes, Gon?alo J. L.
-
supporting information
p. 10128 - 10131
(2019/08/30)
-
- Scaffold Morphing To Identify Novel DprE1 Inhibitors with Antimycobacterial Activity
-
We report a novel benzimidazole (BI) based DprE1 inhibitor that resulted from scaffold morphing of a 1,4-azaindole series. The clinical progression of the 1,4-azaindole series from our previous work validates the potential of exploring newer chemical enti
- Manjunatha,Shandil, Radha,Panda, Manoranjan,Sadler, Claire,Ambady, Anisha,Panduga, Vijender,Kumar, Naveen,Mahadevaswamy, Jyothi,Sreenivasaiah,Narayan, Ashwini,Guptha, Supreeth,Sharma, Sreevalli,Sambandamurthy, Vasan K.,Ramachandran, Vasanthi,Mallya, Meenakshi,Cooper, Christopher,Mdluli, Khisi,Butler, Scott,Tommasi, Ruben,Iyer, Pravin S.,Narayanan, Shridhar,Chatterji, Monalisa,Shirude, Pravin S.
-
supporting information
p. 1480 - 1485
(2019/10/19)
-
- Preparation method of antiviral drug intermediate benzodiazepinone derivative
-
The invention relates to a preparation method of an antiviral drug intermediate and in particular to a preparation method of 7-hydroxyl-5-(1H-pyrrole-2-yl)-1H-benzo[e][1,4]-diaza-2(3H)-one. The preparation method comprises the following steps: by taking 2-amino-5-methoxyl benzoic acid as a raw material, opening a pyrrole ring by applying a Grignard reagent after acetic acid cyclization; removing acetate under the action of sodium hydroxide to obtain an amino functional group compound (II); combining the compound (II) with chloroacetyl chloride; performing a substitution reaction under the action of ammonia water to convert chlorine into an amine compound (V); and closing the ring of the compound (V) through trimethylacetic acid and forming 7-hydroxyl-5-(1H-pyrrole-2-yl)-1H-benzo[e][1,4]-diaza-2(3H)-one (VII) under the action of boron tribromide. The invention provides a brand new compound and a synthetic route for the antiviral drug activity intermediate; the reaction steps are easily controlled, and stable industrial production and preparation can be realized.
- -
-
Paragraph 0011; 0030; 0031
(2017/08/29)
-
- Enantioselective Synthesis of 3-Arylquinazolin-4(3H)-ones via Peptide-Catalyzed Atroposelective Bromination
-
We report the development of a tertiary amine-containing β-turn peptide that catalyzes the atroposelective bromination of pharmaceutically relevant 3-arylquinazolin-4(3H)-ones (quinazolinones) with high levels of enantioinduction over a broad substrate scope. The structure of the free catalyst and the peptide-substrate complex were explored using X-ray crystallography and 2D-NOESY experiments. Quinazolinone rotational barriers about the chiral anilide axis were also studied using density functional theory calculations and are discussed in light of the high enantioselectivities observed. Mechanistic studies also suggest that the initial bromination event is stereodetermining, and the major monobromide intermediate is an atropisomerically stable, mono-ortho-substituted isomer. The observation of stereoisomerically stable monobromides stimulated the conversion of the tribromide products to other atropisomerically defined products of interest. For example, (1) a dehalogenation Suzuki-Miyaura cross-coupling sequence delivers ortho-arylated derivatives, and (2) a regioselective Buchwald-Hartwig amination procedure installs para-amine functionality. Stereochemical information was retained during these subsequent transformations.
- Diener, Matthew E.,Metrano, Anthony J.,Kusano, Shuhei,Miller, Scott J.
-
supporting information
p. 12369 - 12377
(2015/10/12)
-
- BROMODOMAIN-INHIBITING COMPOUNDS AND PHARMACEUTICAL COMPOSITION COMPRISING SAME FOR PREVENTING OR TREATING A CANCER
-
Provided is a novel compound having bromodomain and extra terminal domain (BET) protein inhibiting activities, and a pharmaceutical composition comprising the same which can be useful for prevention or treatment of precancerous transformation or cancer.
- -
-
Page/Page column 23; 26
(2015/11/27)
-
- Benzenesulfonamides incorporating bulky aromatic/heterocyclic tails with potent carbonic anhydrase inhibitory activity
-
Three series of sulfonamides incorporating long, bulky tails were obtained by applying synthetic strategies in which substituted anthranilic acids, quinazolines and aromatic sulfonamides have been used as starting materials. They incorporate long, bulky diamide-, 4-oxoquinazoline-3-yl- or quinazoline-4-yl moieties in their molecules, and were investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides showed excellent inhibitory effects against the four isoforms, with KIs of 7.6-322 nM against hCA I, of 0.06-85.4 nM against hCA II; of 6.7-152 nM against hCA IX and of 0.49-237 nM against hCA XII; respectively. However no relevant isoform-selective behavior has been observed for any of them, although hCA II and XII, isoforms involved in glaucoma-genesis were the most inhibited ones. The structure-activity relationship for inhibiting the four CAs with these derivatives is discussed in detail.
- Bozdag, Murat,Alafeefy, Ahmed M.,Vullo, Daniela,Carta, Fabrizio,Dedeoglu, Nurcan,Al-Tamimi, Abdul-Malek S.,Al-Jaber, Nabila A.,Scozzafava, Andrea,Supuran, Claudiu T.
-
p. 7751 - 7764
(2015/12/20)
-
- NOVEL PROCESS
-
A compound or a pharmaceutically acceptable salt or solvate thereof with a molecular weight in the range 100 to 750 which inhibits the binding of the first and/or second bromodomains of human BRD-2 to 4 to acetylated lysine residues of their physiological partner which is able to: a) form a hydrogen bonding interaction in which the compound accepts a hydrogen bond from the sidechain NH2 group of the asparagine residue found at: or b) accept a water-mediated hydrogen bond in which the compound accepts a hydrogen bond from a water that is itself hydrogen-bonded to the sidechain hydroxyl of the tyrosine residue found at and c) which are also able to form a Van der Waals interaction with a lipophilic binding region of a binding pocket such that one or more heavy atoms of the said compounds lie within a 5A range of any of the heavy atoms of the following bromodomain residues which define the binding pocket: for use in the treatment of chronic autoimmune and inflammatory conditions, acute inflammatory conditions or cancer.
- -
-
Paragraph 0151; 0152
(2015/12/31)
-
- Tetrahydroquinoline Derivatives Useful As Bromodomain Inhibitors
-
Tetrahydroquinoline derivatives, pharmaceutical compositions containing such compounds and to their use in therapy.
- -
-
Paragraph 0231-0232
(2014/02/16)
-
- 7-(3,5-Dimethyl-4-Isoxazolyl)-8-(Methyloxy)-1H-Imidazo[4,5-C]Quinoline Derivatives
-
Novel quinoline compounds pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Paragraph 0285-0286
(2014/03/21)
-
- TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS BROMODOMAIN INHIBITORS
-
Tetrahydroquinoline compounds pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Paragraph 0288
(2014/03/25)
-
- Benzodiazepine Bromodomain Inhibitor
-
The present invention relates to a benzodiazepine compound of formula (I), processes for its preparation, pharmaceutical compositions containing such a compound and to its use in therapy.
- -
-
Page/Page column 14
(2012/09/10)
-
- Condensed Azepine Derivatives As Bromodomain Inhibitors
-
Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 45; 46
(2012/08/27)
-
- Tetrahydroquinoline Derivatives And Their Pharmaceutical Use
-
Tetrahydroquinoline compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 88
(2012/08/28)
-
- Imidazo [4, 5-C] Quinoline Derivatives As Bromodomain Inhibitors
-
Novel compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 90
(2012/09/22)
-
- TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS BROMODOMAIN INHIBITORS
-
Tetrahydroquinoline (I) derivatives, pharmaceutical compositions containing such compounds and to their use in therapy.
- -
-
Page/Page column 50
(2012/11/07)
-
- TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS BROMODOMAIN INHIBITORS
-
Tetrahydroquinoline compounds (I), pharmaceutical compositions containing such compounds and their use in therapy
- -
-
Page/Page column 109-110
(2012/11/07)
-
- DIHYDROQUINOLINE DERIVATIVES AS BROMODOMAIN INHIBITORS
-
Tetrahydroquinoline compounds pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 39-40
(2012/11/14)
-
- NOVEL COMPOUNDS
-
Novel quinoline compounds pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 56
(2012/11/07)
-
- BENZODIAZEPINE BROMODOMAIN INHIBITOR
-
The present invention relates to a benzodiazepine compound of formula (I), processes for its preparation, pharmaceutical compositions containing such a compound and to its use in therapy.
- -
-
Page/Page column 31
(2011/06/11)
-
- BENZODIAZEPINE BROMODOMAIN INHIBITOR
-
Benzodiazepine compounds of formula (I), and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy, in particular in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.
- -
-
Page/Page column 52-53
(2011/06/11)
-
- CONDENSED AZEPINE DERIVATIVES AS BROMODOMAIN INHIBITORS
-
Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 85-86
(2011/06/11)
-
- IMIDAZO [4, 5-C] QUINOLINE DERIVATES AS BROMODOMAIN INHIBITORS
-
Novel compounds of Formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 130-131
(2011/06/11)
-
- TETRAHYDROQUINOLINE DERIVATIVES AND THEIR PHARMACEUTICAL USE
-
Tetrahydroquinoline compounds of Formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 187
(2011/06/11)
-
- THETRAHYDROQUINOLINES DERIVATIVES AS BROMODOMAIN INHIBITORS
-
Tetrahydroquinoline compounds of formula (I) or a salt thereof, pharmaceutical compositions containing such compounds and their use in therapy, in particular in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.
- -
-
Page/Page column 178
(2011/06/11)
-
- BENZOTRIAZOLODIAZEPINE COMPOUNDS INHIBITORS OF BROMODOMAINS
-
Benzodiazepine compounds, pharmaceutical compositions containing such compounds and to their use in therapy.
- -
-
Page/Page column 49
(2012/01/13)
-
- Quinazolin-4-one derivatives: A novel class of noncompetitive NR2C/D subunit-selective N-methyl-D-aspartate receptor antagonists
-
We describe a new class of subunit-selective antagonists of N-methyl d-aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives is noncompetitive and voltage-independent, suggesting that this family of compounds does not exert action on the agonist binding site of the receptor or block the channel pore. The compounds described here resemble CP-465,022 ((S)-3-(2-chlorophenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl] -6-fluoro-3H-quinazolin-4-one), a noncompetitive antagonist of AMPA-selective glutamate receptors. However, modification of ring substituents resulted in analogues with greater than 100-fold selectivity for recombinant NMDA receptors over AMPA and kainate receptors. Furthermore, within this series of compounds, analogues were identified with 50-fold selectivity for recombinant NR2C/D-containing receptors over NR2A/B containing receptors. These compounds represent a new class of noncompetitive subunit-selective NMDA receptor antagonists.
- Mosley, Cara A.,Acker, Timothy M.,Hansen, Kasper B.,Mullasseril, Praseeda,Andersen, Karen T.,Le, Phuong,Vellano, Kimberly M.,Br?uner-Osborne, Hans,Liotta, Dennis C.,Traynelis, Stephen F.
-
supporting information; experimental part
p. 5476 - 5490
(2010/11/16)
-
- Synthesis, structure-activity relationships, and biological profiles of a quinazolinone class of histamine H3 receptor inverse agonists
-
A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H3 receptor inverse agonists. 2-Methyl-3-(4-{[3-(1- pyrrolidinyl)propyl]oxy}phenyl)-5-(trifluoromethyl)-4(3H)-quinazolinone (1) was identified as a promising derivative for further evaluation following optimization of key parameters. Compound 1 has potent H3 inverse agonist activity and excellent selectivity over other histamine receptor subtypes and a panel of 115 unrelated diverse binding sites. Compound 1 also shows satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Two hours after oral administration of 30 mg/kg of 1 to SD rats, significant elevation of brain histamine levels was observed where the brain H3 receptor was highly occupied (>90%). On the basis of species differences in P-glycoprotein (P-gp) susceptibility of 1 between human and rodent P-gps, the observed rodent brain permeability of 1 is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible. The potential of 1 to be an efficacious drug was demonstrated by its excellent brain penetrability and receptor occupancy in P-gp-deficient CF-1 mice.
- Nagase, Tsuyoshi,Mizutani, Takashi,Ishikawa, Shiho,Sekino, Etsuko,Sasaki, Takahide,Fujimura, Takashi,Ito, Sayaka,Mitobe, Yuko,Miyamoto, Yasuhisa,Yoshimoto, Ryo,Tanaka, Takeshi,Ishihara, Akane,Takenaga, Norihiro,Tokita, Shigeru,Fukami, Takehiro,Sato, Nagaaki
-
supporting information; experimental part
p. 4780 - 4789
(2009/07/25)
-
- Fused ring 4-oxopyrimidine derivative
-
The present invention provides a compound represented by formula (I) below, or a pharmaceutically acceptable salt thereof, which, having histamine H3 receptor antagonist or inverse agonist activity, is useful in the prophylaxis or therapy of metabolic diseases, circulatory diseases, or nervous system diseases. [where, for example, Ar is a divalent group formed by eliminating two hydrogen atoms from benzene, X1 is a nitrogen atom, sulfur atom or oxygen atom, R1 is a 5- to 6-membered heteroaryl group, Ring A is a 5- to 6-membered heteroaryl ring, R2 and R3 are amino groups or alkylamino groups, and X2 is represented by formula (II): (where R4 and R5 are lower alkyl groups, and n is an integer from 2 to 4).]
- -
-
Page/Page column 59
(2008/06/13)
-