- SYNTHESIS OF A SICKLE CELL DISEASE AGENT AND INTERMEDIATES THEREOF
-
New processes for preparing 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5- yl)pyridin-3-yl)methoxy)benzaldehyde, an agent developed for the treatment of sickle cell disease, and intermediates thereof, are provided herein.
- -
-
Page/Page column 26-27
(2021/11/13)
-
- Synthesis method of imazapyracid
-
The invention relates to a synthesis method of imazapyracid, relates to a preparation method of a compound, and in particular, relates to a production and synthesis method of imazapyracid; the methodis characterized by comprising the steps: taking quinolinic acid as a raw material and reacting with acetic anhydride to generate 2,3-pyridine dicarboxylic anhydride; and under a low-temperature condition, continuously reacting with alcohol to generate a compound represented by a structural formula (I), carrying out a ring closing reaction with 2-amino-2,3-dimethylbutyramide under an alkaline condition, extracting to adjust the pH value, and thus obtaining the imazapyracid product. The method has the advantages that a novel method for obtaining imazapyracid is provided, the route reaction speed is high, the product purity is extremely high, the yield is high, the reaction conditions are mild, isomers are avoided, catalysts are not needed, three wastes are few, the synthesis process is extensive, the reaction conditions are optimized, the reaction equipment cost is reduced, generated products are easy to separate, and the production process is simplified.
- -
-
-
- IDO/TDO Inhibitor
-
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, an aliphatic ring and a heterocyclic ring; X, R1 and R2 represent a substituent on a ring atom constituting ring A; m represents an integer of 0 to 6; X represents, for example, a halogen atom; and R1 and R2 are the same or different and are selected from, for example, the group consisting of groups of formula (a) or formula (b); and in the following formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1 to 8, r represents an integer of 1 to 8, s represents an integer of 1 to 8, R4 represents, for example, —C(═NH)—HN2, and R6 represents, for example, a substituted or unsubstituted aryl group].
- -
-
Paragraph 0869-0872
(2020/08/19)
-
- AZA-A-RING INDENOISOQUINOLINE TOPOISOMERASE I POISONS
-
The invention described herein pertains to four series of aza-A-ring indenoisoquinolines, which are inhibitors of topoisomerase IB (Top1), and the processes for preparing said aza-A-ring indenoisoquinolines. Also described are methods for treating cancer
- -
-
Paragraph 00107; 00136
(2017/10/13)
-
- Investigation of the Structure-Activity Relationships of Aza-A-Ring Indenoisoquinoline Topoisomerase i Poisons
-
Several indenoisoquinolines have shown promise as anticancer agents in clinical trials. Incorporation of a nitrogen atom into the indenoisoquinoline scaffold offers the possibility of favorably modulating ligand-binding site interactions, physicochemical properties, and biological activities. Four series of aza-A-ring indenoisoquinolines were synthesized in which the nitrogen atom was systematically rotated through positions 1, 2, 3, and 4. The resulting compounds were tested to establish the optimal nitrogen position for topoisomerase IB (Top1) enzyme poisoning activity and cytotoxicity to human cancer cells. The 4-aza compounds were the most likely to yield derivatives with high Top1 inhibitory activity. However, the relationship between structure and cytotoxicity was more complicated since the potency was influenced strongly by the side chains on the lactam nitrogen. The most cytotoxic azaindenoisoquinolines 45 and 46 had nitrogen in the 2- or 3-positions and a 3′-dimethylaminopropyl side chain, and they had MGM GI50 values that were slightly better than the corresponding indenoisoquinoline 64.
- Beck, Daniel E.,Reddy, P. V. Narasimha,Lv, Wei,Abdelmalak, Monica,Tender, Gabrielle S.,Lopez, Sophia,Agama, Keli,Marchand, Christophe,Pommier, Yves,Cushman, Mark
-
p. 3840 - 3853
(2016/05/24)
-
- A practical strategy for the structural diversification of aliphatic scaffolds through the palladium-catalyzed picolinamide-directed remote functionalization of unactivated C(sp3)-H bonds
-
Hats off to the director: High levels of regio- and stereoselectivity were observed for a broad range of amine substrates with aryl and vinyl iodide coupling partners in the title reaction. The synthetic utility of this strategy was highlighted by the rea
- He, Gang,Chen, Gong
-
supporting information; experimental part
p. 5192 - 5196
(2011/06/26)
-
- 4-MORPHOLINO-PYRIDO[3,2-D]PYRIMIDINES
-
This invention relates to compounds of Formula (I) as Pi3k inhibitors for treating autoimmune deseases, inflammatory disorders, multiple sclerosis and other deseases like cancers.
- -
-
Page/Page column 59-60
(2010/04/27)
-
- Synthesis and antiviral activity of 7-benzyl-4-hydroxy-1,5-naphthyridin- 2(1H)-one HIV integrase inhibitors
-
The medicinal chemistry and structure-activity relationships for a novel series of 7-benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naph
- Boros, Eric E.,Edwards, Cynthia E.,Foster, Scott A.,Fuji, Masahiro,Fujiwara, Tamio,Garvey, Edward P.,Golden, Pamela L.,Hazen, Richard J.,Jeffrey, Jerry L.,Johns, Brian A.,Kawasuji, Takashi,Kiyama, Ryuichi,Koble, Cecilia S.,Kurose, Noriyuki,Miller, Wayne H.,Mote, Angela L.,Murai, Hitoshi,Sato, Akihiko,Thompson, James B.,Woodward, Mark C.,Yoshinaga, Tomokazu
-
experimental part
p. 2754 - 2761
(2010/01/16)
-
- SUBSTITUTED HETEROCYCLES AND THEIR USE AS CHK1, PDK1 AND PAK INHIBITORS
-
This invention relates to novel compounds of Formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds possess CHK1 kinase inhibitory activity, PDK1 inhibitory activity and Pak kinase inhibitory activity and are accordingly useful in the treatment and/or prophylaxis of cancer.
- -
-
Page/Page column 129
(2008/06/13)
-
- Efficient access to novel mono- and disubstituted pyrido[3,2-d]pyrimidines
-
New mono- and disubstituted pyrido[3,2-d]pyrimidines were synthesized starting from the corresponding 2,4-dichloro derivative through SNAr and palladium-catalyzed reactions. SNAr and palladium-catalyzed hydro-deshalogenation occurred
- Tikad, Abdellatif,Routier, Sylvain,Akssira, Mohamed,Leger, Jean-Michel,Jarry, Christian,Guillaume, Gérald
-
p. 1938 - 1942
(2008/02/08)
-
- Structure-based design and synthesis of macroheterocyclic peptidomimetic inhibitors of the aspartic protease β-site amyloid precursor protein cleaving enzyme (BACE)
-
Based on the X-ray cocrystal structure of the Tang-Ghosh heptapeptide inhibitor 1 (OM00-3), a series of macroheterocyclic analogues were designed and synthesized. Analogues containing dithia, dioxa, oxathia, and carbathia macrocycles were synthesized by m
- Hanessian, Stephen,Yang, Gaoqiang,Rondeau, Jean-Michel,Neumann, Ulf,Betschart, Claudia,Tintelnot-Blomley, Marina
-
p. 4544 - 4567
(2007/10/03)
-
- 1,6- And 1,7-naphthyridines. IV. Synthesis of hydroxycarboxamide derivatives
-
A series of 8-hydroxy-1,6-naphthyridin-5(6H)-one-7-carboxamides 1 and the isomeric 5-hydroxy-1,7-naphthyridin-8(7H)-one-6-carboxamides 2 were synthesized. N-Lactam unsubstituted compounds 1a-c and 2a,b were obtained by alkoxide-induced rearrangement of the corresponding quinolinimidoacetamides 3. Compounds 1e,f and 2e,f were synthesized by heterocyclization of the corresponding quinolinamic esters 6 and 7. Spectroscopic properties (uv, ir, 1H and 13C nmr and ms) were analyzed and the proposed structures confirmed.
- Blanco, M. Mercedes,Schapira, Celia B.,Levin, Gustavo,Perillo, Isabel A.
-
p. 493 - 502
(2007/10/03)
-
- Efficient synthesis of novel pyrido[3,2-d]pyrimidine-2,4-diones
-
A series of pyrido[3,2-d]pyrimidine-2,4-diones 5a-g have been synthesized through conversion of 2,3-pyridinedicarboxylic anhydride 1 into half-ester 2, subsequent Curtius rearrangement and further reaction with amino acids.
- Mamouni,Aadil,Akssira,Lasri,Sepulveda-Arques
-
p. 2745 - 2747
(2007/10/03)
-
- Benzopyridazinone and pyridopyridazinone compounds
-
Benzo or pyridopyridazinones and pyridazinthiones of the formula STR1 wherein: X and Y are nitrogen or carbon, provided that at least one is carbon, and Z is oxygen or sulfur; R1 is hydrogen, lower alkyl, aryl, aralkyl, heterocyclo, heterocyclo lower-alkyl, heteroaryl, or heteroaralkyl; R2, R3, R4, R5 and R6 are independently selected from hydrogen, lower alkyl, halo, carboxy, alkoxycarbonyl, carbamoyl, lower-alkyl carbonyl, halocarbonyl, thiomethyl, trifluoromethyl, cyano or nitro; or a pharmaceutically acceptable ester, ether or salt thereof, have been found to be useful as an anti-inflammatory, antasthmatic, immunosuppressive, anti-allograft rejection, anti-graft-vs-host rejection, autoimmune disease or analgetic agent(s).
- -
-
-
- Synthesis of the Pyridine Analogues of Phthalide
-
Routes for the preparation of the four isomeric pyridine analogues of phthalide are described starting from the readily available pyridine 2,3- and 3,4-diacids, or derivatives, and making use of the differential reactivity of substituents at pyridine 2- versus 3- and 3- versus 4-positions.
- Ashcroft, William R.,Beal, Michael G.,Joule, John A.
-
p. 3012 - 3015
(2007/10/02)
-
- PREPARATION AND STRUCTURAL ASSIGNMENTS OF SOME ISOMERIC 2,3-DISUBSTITUTED PYRIDINES
-
The preparation of several isomeric 2,3-disubstituted pyridine compounds are described and their spectroscopical data given.IR and NMR spectra of quinolinimide, reported by Distefano et al., are contradicted.The electron impact mass spectra are found to be useful in the differentiation between positional isomers.
- Spiessens, Luc I. M.,Anteunis, Marc J. O.
-
p. 205 - 232
(2007/10/02)
-
