- Benzo[b]thiophene-based histone deacetylase inhibitors
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Benzo[b]thienyl hydroxamic acids, a novel class of histone deacetylase (HDAC) inhibitors, were identified via a targeted screen of small molecule hydroxamic acids. Various substitutions were explored in the C5- and C6-positions of the benzo[b]thiophene co
- Witter, David J.,Belvedere, Sandro,Chen, Liqiang,Secrist, J. Paul,Mosley, Ralph T.,Miller, Thomas A.
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p. 4562 - 4567
(2008/02/11)
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- BENZOTHIOPHENE DERIVATIVES
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The present invention relates to a novel class of benzothiophene amide derivatives. The hydroxamic acid compounds can be used to treat cancer. The benzothiophene amide compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.
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- BENZOTHIOPHENE HYDROXAMIC ACID DERIVATIVES
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The present invention relates to a novel class of hydroxamic acid derivatives. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing t
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- Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides
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The synthesis of a novel series of potent inhibitors of histone deacetylases is described, based on arylsulfinyl-2,4-hexadienoic acid hydroxyamicles and their derivatives. In vitro IC50 values clown to 40 nM were obtained, and several compounds showed inhibition of CEM (human leukemic) cell viability with IC50 of ～1.5 μM, comparable to or better than that of suberoylatiilide hydroxamic acid, an inhibitor of histone cleacetylase currently in clinical trials.
- Marson, Charles M.,Savy, Pascal,Rioja, Alphonse S.,Mahadevan, Thevaki,Mikol, Catherine,Veerupillai, Arthi,Nsubuga, Eva,Chahwan, Angela,Joel, Simon P.
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p. 800 - 805
(2007/10/03)
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- Inhibitors of soluble adenylate cyclase
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The invention relates to compounds of general Formula I, the production thereof, and the use thereof as a medicinal product.
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Page/Page column 7-8
(2008/06/13)
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- BENZOTHIOPHENE HYDROXAMIC ACID DERIVATIVES WITH CARBAMATE, UREA, AMIDE AND SULFONAMIDE SUBSTITUTIONS
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The present invention relates to a novel class of hydroxamic acid derivatives carbamate, urea, amide and sulfonamide substitutions. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit histone deacetyla
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Page/Page column 44
(2008/06/13)
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- EP2 RECEPTOR AGONISTS
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A compound of Formula (I) or a salt, solvate and chemically protected form thereof, wherein: R5 is an optionally substituted C5-20 aryl or C4-20 alkyl group; A is selected from the group consisting of Formulae (Ai), (Aii), (Aiii) D is selected from Formulae (Di), (Dii), (Diii), (Div), (Dv) B is selected from the group consisting of Formulae (Bi), (Bii), (Biii), (Biv) (Bv).
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Page/Page column 146
(2008/06/13)
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- THIOPHENE AND BENZOTHIOPHENE HYDROXAMIC ACID DERIVATIVES
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The present invention relates to a novel class of hydroxamic acid derivatives having a benzothiophene or thiophene backbone. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit historic deacetylase and
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Page/Page column 94; 95
(2008/06/13)
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- Novel benzothienyl or indole derivatives, preparation and use thereof as inhibitors of prenyl transferase proteins
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The invention concerns compounds of general formula (1), wherein, in particular; W represents H, SO2R5. CO(CH2)nR5, (CH2)nR6, CS(CH2)nR5; X represents S or NH; Y represents (CH2)p, CO, (CH2)pCO, CH═CH—CO; Z represents a hetcrocycle, imidazole, benzimidazole, isoxazole, tetrazole, oxadiazole, thiadazole, pyridine, quinazoline, quinoxaline, quinoline, thiophene; R1 represents COOR6, CONR6R7, CO—NH—CH(R6)—COOR7, CH2NR6R7, CH2OR6, (CH2)pR6, CH═CHR6; R2 represents in particular hydrogen, C1-C10 alkyl, a substituted or unsubstituted phenyl; R5 and R6 represents hydrogen, C1—C6 alkyl; R5 represents a substituted or unsubstituted phenyl or naphthyl; R6 and R7, identical or different, represent hydrogen, C1—C15 alkyl, a hetcrocycle. an aryl; n represents 0 to 10; p represents 1 to 6.
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- HISTONE DEACETYLASE INHIBITORS
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The present invention provides histone deacetylase inhibitors of general formula (I), process for the preparation of such compounds and uses of the compounds in medicine.
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- Peptide derivatives useful in treating autoimmune diseases
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PCT No. PCT/GB97/00438 Sec. 371 Date Aug. 20, 1998 Sec. 102(e) Date Aug. 20, 1998 PCT Filed Feb. 18, 1997 PCT Pub. No. WO97/31023 PCT Pub. Date Aug. 28, 1997The invention concerns pharmaceutically useful peptide derivatives of the formula (I): P-R1-R2-R3-R4, in which P, R1, R2, R3, and R4 have the various meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel peptide derivatives are of value in treating MHC class II dependent T-cell mediated autoimmune or inflammatory diseases, such as rheumatoid arthritis. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds in medical treatment.
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- Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives
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A novel series of platelet receptor glycoprotein (Gp) IIb/IIIa antagonists with condensed heterocycles as their basic core was synthesized. In an in vitro assay, trans-4-(5-amidinobenzofuran-2- carboxamido)cyclohexyl]oxyacetic acid 17e and trans-3-[4-(5-
- Ono, Shin'ichiro,Yoshida, Tomohiro,Maeda, Kazuhiro,Kosaka, Keigo,Inoue, Yoshihisa,Imada, Teruaki,Fukaya, Chikara,Nakamura, Norifumi
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p. 1694 - 1712
(2007/10/03)
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- Practical Synthesis of Optically Pure Bifunctionalized Heterohelicenes
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Optically active 2-(hydroxymethyl)- and 2-(ethylthiocarbonyl)[1]benzothieno[5′,4′ :2.3][1]benzothieno [4′.5 :4,5]-thieno[3,2-f]quinolines containing π-excessive thiophene and π-deficient pyridine units were prepared by the use of exo-3-amino-2-hydroxybornane as a chiral auxiliary. This procedure consists of separation of the helical diastereomers prepared by photocyclization of 1,2-diarylethylenes and removal of the chiral auxiliary by a thiolate ion. Large scale preparation of the helicenes can be accomplished by a modified procedure of the photocyclization reaction. Optical purities of both enantiomers of 2-(hydroxymethyl)- and 2-(ethylthiocarbonyl)[1] benzothieno[5′ ,4′ : 2,3][I]benzothieno[4′.5′ : 4,5]-thieno[3,2-f lquinolines were >99.5%. Their absolute configurations were determined by comparison of CD spectra.
- Osuga, Hideji,Suzuki, Hitomi,Tanaka, Kazuhiko
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p. 891 - 897
(2007/10/03)
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- Synthesis and crystal structure of chiral bifunctional helicenes with π-deficient pyridine and π-excessive thiopene units
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Both enantiomers of new bifunctional helicenes constructed from π-excessive 2-(hydroxymethyl)thiophene and π-deficient pyridine rings have been prepared using (1R, 2S, 3R, 4S)-3-amino-2-hydroxybornane as a chiral auxiliary. The X-ray crystal structure reveals the intermolecular hydrogen bond between the hydroxy group of the helicene and the pyridine nitrogen atom of the adjacent molecule. The non-bonded distance between the nitrogen atom and the oxygen atom is 2.72 A, and the interplanar angle between the terminal rings is 45.3°.
- Tanaka, Kazuhiko,Kitahara, Yoshinori,Suzuki, Hitomi,Osuga, Hideji,Kawai, Yasushi
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p. 5925 - 5928
(2007/10/03)
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- 1,2,3-triazolo compounds
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Heterocyclic dihydroxyquinoxaline compounds having the formula STR1 wherein R 2 is hydrogen, NO 2, NH 2, CN, halogen, or SO 2 NH 2 ; --X--Y--Z-- is selected from --N N--N 3 --,--NR 3 --N N--, N--NR 3 --N , wherein R 3 is hydrogen, lower alkyl, or CF 3.The invention also relates to a method of preparing the compounds, pharmaceutical compositions thereof, and their use.The compounds are useful in the treatment of indications caused by hyperactivity of the excitatory neurotransmitters.
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