- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF 1H-PYRAZOLO[4,3-B]PYRIDINES
-
The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors together with a second compound useful in the treatment of a neurodegenerative disorder and their combined use as a medicament, in particular for the treatment of neurodegenerative and/or cognitive disorders.
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Page/Page column 105
(2019/07/19)
-
- MACROCYCLES AS PDE1 INHIBITORS
-
The present invention provides macrocycles of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
- -
-
Paragraph 0214; 0215
(2019/06/30)
-
- 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
-
The present invention provides 1H-pyrazolo[4,3-b]pyridines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
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-
Paragraph 0494-0495
(2019/07/10)
-
- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF 1H-PYRAZOLO[4,3-B]PYRIDINES
-
The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors together with a second compound which compound is useful in the treatment of a psychiatric disorder and their combined use as a medicament, in particular for the treatment of psychiatric and/or cognitive disorders.
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-
Page/Page column 102
(2019/07/19)
-
- 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
-
The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
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-
Page/Page column 96; 97
(2018/09/25)
-
- The Total Synthesis of Epothilone D as a Yardstick for Probing New Methodologies
-
Here, a concise and highly convergent synthesis of epothilone D was investigated, relying on fragments of equal complexity that could be prepared in gram scale quantities. The strategy to construct the fragments includes the use of a previously reported enantiospecific zinc-catalyzed cross-coupling of an α-hydroxy ester triflate with a Grignard reagent, the application of a hydroboration/boron–magnesium exchange sequence for the rapid construction of the Z-substituted trisubstituted double bond present in the natural product, and a Noyori-type hydrogenation to install the β-hydroxy ester moiety of the southern part. The key to success is the diastereoselective head-to-tail macrolactonization by an intramolecular addition of the corresponding ω-alkynyl-substituted carboxylic acids to construct a new stereocenter in the macrocyclic core structure in one single step.
- Haydl, Alexander M.,Breit, Bernhard
-
supporting information
p. 541 - 545
(2017/01/18)
-
- QUINAZOLINE DERIVATIVE
-
Provided are a quinazoline derivative, a pharmaceutical composition containing the same, a method for preparation of said derivative, and an application of same as an anti-cancer drug.
- -
-
Paragraph 0093
(2017/07/04)
-
- NOVEL COMPOUND, ORGANIC CATION TRANSPORTER 3 DETECTION AGENT, AND ORGANIC CATION TRANSPORTER 3 ACTIVITY INHIBITOR
-
[Problem] The present invention addresses the problem of providing a novel compound. The present invention also addresses the problem of providing an OCT3 detection agent or an OCT3 activity inhibitor, which comprises the novel compound. [Solution] A compound represented by formula (A), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof. ????????R1-R2-R3-R4?????(A)
- -
-
Paragraph 0851-0853
(2016/08/17)
-
- SYNTHETIC PRECURSOR OF EPOTHILONE FOR IMPROVING PRODUCTION OF EPOTHILONE AND METHOD FOR PREPARING EPOTHILONE USING THE SAME
-
The present invention relates to a compound for increasing production of epothilone in actinomyces, and to a method for producing epothilone with increased yield. The method for producing epothilone of the present invention includes a step of culturing actinomyces in which epothilone-biosynthesizing genes in Sorangium cellulosum including epoD, epoE, epoF, orf6, orf3, and orf14 are introduced in a culture medium. According to the present invention, it is possible to increase the production yield of epothilone in actinomyces, even in actinomyces in which epoA, epoP, epoB, and epoC are not introduced therein.COPYRIGHT KIPO 2016
- -
-
Paragraph 0067; 0068; 0069
(2016/10/10)
-
- Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350)
-
The HIV protease inhibitor (PI) ritonavir (RTV) has been widely used as a pharmacoenhancer for other PIs, which are substrates of cytochrome P450 3A (CYP3A). However the potent anti-HIV activity of ritonavir may limit its use as a pharmacoenhancer with other classes of anti-HIV agents. Ritonavir is also associated with limitations such as poor physicochemical properties. To address these issues a series of compounds with replacements at the P2 and/or P3 region was designed and evaluated as novel CYP3A inhibitors. Through these efforts, a potent and selective inhibitor of CYP3A, GS-9350 (cobicistat) with improved physiochemical properties was discovered.
- Xu, Lianhong,Liu, Hongtao,Hong, Allen,Vivian, Randy,Murray, Bernard P.,Callebaut, Christian,Choi, You-Chul,Lee, Melody S.,Chau, Jennifer,Tsai, Luong K.,Stray, Kirsten M.,Strickley, Robert G.,Wang, Jianhong,Tong, Leah,Swaminathan, Swami,Rhodes, Gerry R.,Desai, Manoj C.
-
p. 995 - 999
(2014/02/14)
-
- TETRA-SUBSTITUTED NDGA DERIVATIVES VIA ETHER BONDS AND CARBAMATE BONDS AND THEIR SYNTHESIS AND PHARMACEUTICAL USE
-
Disclosed are nordihydroguaiaretic acid derivative compounds including various end groups bonded by a carbon atom or heteroatom though a side chain bonded to the respective hydroxy residue O groups by an ether bond or a carbamate bond, pharmaceutical compositions, methods of making them, and methods of using them and kits including them for the treatment of diseases and disorders, in particular, diseases resulting from or associated with a virus infection, such as HIV infection, HPV infection, or HSV infection, an inflammatory disease, such as various types of arthritis and inflammatory bowel diseases, a metabolic disease, such as diabetes, a vascular disease, such as hypertension and macular degeneration, or a proliferative disease, such as diverse types of cancers.
- -
-
Paragraph 0107; 0146
(2013/11/19)
-
- OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
-
The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.
- -
-
Page/Page column 84
(2012/05/05)
-
- Tandem synthesis and in vitro antiplasmodial evaluation of new naphtho[2,1-d]thiazole derivatives
-
A series of naphtho[2,1-d]thiazoles was prepared in good yields under microwave irradiation with an original protocol combining tandem direct arylation and intramolecular Knoevenagel reaction on 1,3-thiazole derivatives. Antiplasmodial evaluation of this
- Cohen, Anita,Verhaeghe, Pierre,Crozet, Maxime D.,Hutter, Sébastien,Rathelot, Pascal,Vanelle, Patrice,Azas, Nadine
-
p. 315 - 324
(2012/11/07)
-
- EPOTHILONE ANALOGUES, THEIR PHARMACEUTICAL COMPOSITIONS, THEIR USE AND THEIR PREPA RATIONS
-
The present invention relates to novel 15-membered thiazole lactone or lactam polyketide compounds, their pharmaceutical compositions, their use and their preparations. The disclosed compounds relate to those of general formula I, their preparations and their use for preparing therapeutical compositions used as cell inhibitors.
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-
Page/Page column 21
(2011/05/16)
-
- EPOTHILONE ANALOGUES, THEIR PHARMACEUTICAL COMPOSITIONS, THEIR USE AND THEIR PREPARATIONS
-
The present invention discloses novel Epothilone analogues, their pharmaceutical compositions, their use and their preparations, especially discloses the compounds of general formula I, their preparations and their use for preparing therapeutical compositions used as cell inhibitors.
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-
Page/Page column 25
(2010/12/30)
-
- Synthesis of new 1,4-dihydropyridine derivatives containing thiazolyl substituents
-
A series of 4-[2-methyl (or aryl) thiazole-4-yl]-2,6-dimethyl-3,5-diacetyl (or dibenzoyl) 1,4-dihydropyridines were synthesized using a modified Hantzsch reaction involving the condensation of the corresponding aldehyde with acetyl acetone or benzoyl acetone. The preparation of the corresponding aldehydes (2-methylthiazole-4-carboxaldehyde and some 2-arylthiazole-4-carboxaldehydes) was achieved by a simplified protocol of the published synthesis.
- Bazargan, Leila,Shafiee, Abbas,Amini, Mohsen,Dezfouli, Ebrahim Bakhshi,Azizi, Ebrahim,Ghaffari, Seyed Mahmood
-
experimental part
p. 602 - 609
(2009/10/02)
-
- An efficient aqueous microwave-assisted Suzuki-Miyaura cross-coupling reaction in the thiazole series
-
A new simple, rapid and high yielding synthesis of various 5-substituted thiazoles by Suzuki-Miyaura cross-coupling reaction is described using microwave irradiation in aqueous medium without organic co-solvent in the presence of tetrabutylammonium bromid
- Cohen, Anita,Crozet, Maxime D.,Rathelot, Pascal,Vanelle, Patrice
-
scheme or table
p. 1736 - 1742
(2011/02/27)
-
- PYRAZOLE COMPOUNDS AND USE THEREOF
-
The pyrazole compound of the present invention is represented by the following general formula (I). The pyrazole compound of the present invention or a salt thereof or a solvate thereof potently inhibits liver glycogen phosphorylase, and, therefore, is useful as a therapeutic or prophylactic agent for diabetes. wherein each symbol denotes as described in the specifications.
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-
Page/Page column 53
(2009/05/29)
-
- TETRA-SUBSTITUTED NDGA DERIVATIVES VIA ETHER BONDS AND CARBAMATE BONDS AND THEIR SYNTHESIS AND PHARMACEUTICAL USE
-
Disclosed are nordihydroguaiaretic acid derivative compounds including various end groups bonded by a carbon atom or heteroatom though a side chain bonded to the respective hydroxy residue O groups by an ether bond or a carbamate bond, pharmaceutical compositions, methods of making them, and methods of using them and kits including them for the treatment of diseases and disorders, in particular, diseases resulting from or associated with a virus infection, such as HIV infection, HPV infection, or HSV infection, an inflammatory disease, such as various types of arthritis and inflammatory bowel diseases, a metabolic disease, such as diabetes, a vascular disease, such as hypertension and macular degeneration, or a proliferative disease, such as diverse types of cancers.
- -
-
Page/Page column 28-29
(2008/06/13)
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- TETRA-O-SUBSTITUTED BUTANE-BRIDGE MODIFIED NDGA DERIVATIVES, THEIR SYNTHESIS AND PHARMACEUTICAL USE
-
The present invention relates to nordihydroguaiaretic acid derivative compounds, namely, butane bridge modified nordihydroguaiaretic acid (NDGA) compounds and butane bridge modified tetra-O-substituted NDGA compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them and kits including them for the treatment of diseases and disorders, in particular, diseases resulting from or associated with a virus infection, such as HIV infection, HPV infection, or HSV infection, an inflammatory disease, such as various types of arthritis and inflammatory bowel diseases, metabolic diseases, such as diabetes and hypertension, or a proliferative disease, such as diverse types of cancers.
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-
Page/Page column 33
(2008/06/13)
-
- Design, synthesis, and biological testing of potential heme-coordinating nitric oxide synthase inhibitors
-
Based on computer modeling of the active site of nitric oxide synthases (NOS), a series of 10 amidine compounds (9-18) was designed including potential inhibitors that involve the coordination of side-chain functional groups with the iron of the heme cofactor. The most potent and selective compound was the methylthio amidine analogue 9, which was more potent than l-nitroarginine with 185-fold selectivity for inhibition of neuronal NOS over endothelial NOS. It also exhibited time-dependent inhibition, but did not involve the mechanism previously proposed for other amidine inhibitors of NOS. None of the compounds, however, exhibited heme-binding characteristics according to absorption spectroscopy.
- Litzinger, Elizabeth A.,Martasek, Pavel,Roman, Linda J.,Silverman, Richard B.
-
p. 3185 - 3198
(2007/10/03)
-
- Oximinoarylsulfonamides as potent HIV protease inhibitors
-
The need for a potent HIV protease inhibitor (PI) to combat emerging PI-resistant viruses is anticipated. Analogs formulated from the combination of structural fragments of Ritonavir, Lopinavir, and Amprenavir were synthesized. Analogs containing the oxime pharmacophore were found to have improved activities against both wild type and resistant (A17) viruses. The synthesis and structure-activity relationships (SAR) based upon the in vitro IC50 of this series of compounds are reported.
- Yeung, Clinton M.,Klein, Larry L.,Flentge, Charles A.,Randolph, John T.,Zhao, Chen,Sun, MingHua,Dekhtyar, Tatyana,Stoll, Vincent S.,Kempf, Dale J.
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p. 2275 - 2278
(2007/10/03)
-
- Studies towards the synthesis of epothilone A via organoboranes
-
Studies towards the synthesis of epothilone A via organoboranes have been described. A modified procedure for the large-scale preparation of B-γ,γ-dimethylallyldiisopinocampheylborane from prenyl alcohol has been developed. This reagent, upon reaction wit
- Ramachandran, P. Veeraraghavan,Chandra, J. Subash,Prabhudas, Bodhuri,Pratihar, Debarshi,Reddy, M. Venkat Ram
-
p. 3812 - 3824
(2007/10/03)
-
- HIV protease inhibiting compounds
-
A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
- -
-
Page/Page column 146; 147
(2010/02/12)
-
- Total syntheses of epothilones B and D
-
A convergent, total synthesis of epothilones B (2) and D (4) is described. The key steps are Normant coupling to establish the desired (Z)-stereochemistry at C12-C13, Wadsworth-Emmons olefination of methyl ketone 28 with the phosphonate ester 8, diastereoselective aldol condensation of aldehyde 5 with the enolate of keto acid derivatives to form the C6-C7 bond, selective deprotection of acid 52, and macrolactonization.
- Jung, Jae-Chul,Kache, Rajashaker,Vines, Kimberly K.,Zheng, Yan-Song,Bijoy, Panicker,Valluri, Muralikrishna,Avery, Mitchell A.
-
p. 9269 - 9284
(2007/10/03)
-
- 14-Methyl-epothilones
-
The present invention provides 14-methyl epothilone compounds, along with intermediates thereto, methods for their preparation, compositions comprising the compounds, and methods for their use in the treatment of cancer and other diseases and conditions c
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-
-
- Method for producing epothilone B and derivatives, and intermediate products for this method
-
The invention relates to a method for producing epothilone B and derivatives, and to intermediate products for this method. According to the novel method, the epothilone B or derivatives are produced in high yields from the C1-C6, C7-C10 and C11-C20-fragm
- -
-
-
- Intermediates for the synthesis of epothilones and methods for their preparation
-
The invention relates to a method of synthesis for a compound of formula (I), wherein R is a heterocyclyl moiety and X1, X2, X3and X4are, independently of each other, protecting groups, which is appropriate for the synthesis of epothilone B and desoxyepothione B.
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-
Page column 19
(2010/01/30)
-
- Total synthesis of epothilone A through stereospecific epoxidation of the p-methoxybenzyl ether of epothilone C
-
The total synthesis of epothilone A is described by the coupling four segments 4 - 7a. Three of the segments, 4, 5 and 7a, have only one chiral center; all other chiral centers were introduced by simple asymmetric catalytic reactions. The key steps are the ring opening of epoxide 5 with acetylide 8 for the construction of the C12-C13 cis double bond and a practical hydrolytic kinetic resolution (HKR) developed by Jacobsen group for the introduction the chiral center at C3. Especially, the stereospecific epoxidation of 3-O-PMB epothilone C 3b through long-range effect of 3-O-PMB protecting group gave high yields of the C12 - C13 α-epoxide for the synthesis of target molecule.
- Liu, Zhi-Yu,Chen, Ze-G,Yu, Cheng-Zhi,Wang, Rui-Fang,Zhang, Ru-Zhou,Huang, Chu-Sheng,Yan, Zheng,Cao, De-Rong,Sun, Jian-Bo,Li, Gang
-
p. 3747 - 3756
(2007/10/03)
-
- Total Syntheses of Epothilones B and D
-
Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.
- Mulzer, Johann,Mantoulidis, Andreas,Oehler, Elisabeth
-
p. 7456 - 7467
(2007/10/03)
-
- En route to a plant scale synthesis of the promising antitumor agent 12,13-desoxyepothilone B.
-
[reaction--see text] Efficient and processable syntheses of key building blocks of the antitumor agent 12,13-desoxyepothilone B (dEpoB) by catalytic asymmetric induction are herein described.
- Chappell,Stachel,Lee,Danishefsky
-
p. 1633 - 1636
(2007/10/03)
-
- SYNTHETIC APPLICATIONS OF 2-CHLOROOXIRANES: PREPARATION OF THIAZOLES, DIHYDROTHIAZOLES AND SELENAZOLES
-
The reaction of 2-chlorooxiranes 1 with thioamides and thioureas provides access to thiazoles, 4-hydroxy-4,5-dihydrothiazoles and 2-imino-2,3-dihydrothiazoles under mild conditions and excellent yields.With 1 and selenourea, near quantitative yields of se
- Gasteiger, Johann,Herzig, Christian
-
p. 2607 - 2611
(2007/10/02)
-
- PHARMACEUTICAL COMPOSITIONS AND METHODS OF INHIBITING H-1 AND H-2 HISTAMINE RECEPTORS
-
Pharmaceutical compositions and methods of inhibiting H-1 and H-2 histamine receptors by administering an antihistamine and an H-2 histamine receptor inhibitor. Exemplary of the antihistamine in the compositions and methods of this invention is mepyramine and exemplary of the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-2-((4-methyl-5-imidazolyl)-methylthio)ethyl!guanidine. "
- -
-
-
- PHARMACOLOGICALLY ACTIVE GUANIDINE COMPOUNDS
-
The compounds are substituted thioalkyl-, aminoalkyl-and oxyalkyl-guanidines which are inhibitors of histamine activity.
- -
-
-