- HETEROBIFUNCTIONAL MOLECULES AS TEAD INHIBITORS
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The invention relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.
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- Total Synthesis of the 7,10-Epimer of the Proposed Structure of Amphidinolide N, Part I: Synthesis of the C1-C13 Subunit
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Amphidinolide N, the structure of which has been recently revised, is a 26-membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10-epimer of the proposed structure of amphidinolide N, we have synthesized the C1-C13 subunit enantio- and diastereoselectively. Key reactions include an l-proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao-Fleming oxidation. To aid late-stage manipulations, we also developed the 4-(N-benzyloxycarbonyl-N-methylamino)butyryl group as a novel ester protective group for the C9 alcohol.
- Ochiai, Koji,Kuppusamy, Sankar,Yasui, Yusuke,Okano, Tsubasa,Matsumoto, Yasunobu,Gupta, Nishant R.,Takahashi, Yohei,Kubota, Takaaki,Kobayashi, Jun'ichi,Hayashi, Yujiro
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supporting information
p. 3282 - 3286
(2016/03/05)
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- MULTIFUNCTIONAL RADICAL QUENCHERS
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The invention provides a compound of formula (I): [insert formula (I)] wherein X, Y, and R1-R4 have any of the values defined in the specification, and salts thereof, as well as compositions comprising the compounds or salts. The compounds are useful for treating diseases associated with impaired mitochondrial function in an animal.
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- Second-generation process research towards eletriptan: A fischer indole approach
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The development of a second-generation process for the synthesis of eletriptan via a Fischer indole cyclisation is described. The finalised process offers several potential advantages over the current route of manufacture including cost, throughput, and safety.
- Ashcroft, Christopher P.,Pettman, Alan,Watkinson, Simon,Hellier, Paul
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experimental part
p. 98 - 103
(2011/09/16)
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- Urotensin II receptor antagonists
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This invention is directed to a compound of Formula (I): and forms thereof, wherein A, B, E, G, X and L2 are as defined herein and their use as urotensin II receptor antagonists.
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Page/Page column 53
(2009/01/24)
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- Synthesis and evaluation of α,α′-disubstituted phenylacetate derivatives for T-type calcium channel blockers
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We have synthesized and evaluated α,α′-disubstituted phenylacetate derivatives that were designed as T-type calcium channel blockers. Among them, compound 10e (IC50 = 8.17 ± 0.48 nM) showed the most potent T-type calcium current blocking activity and higher potency than Mibefradil (IC50 = 1.34 ± 0.49 μM). The PK profile and subtype selectivity over L-type calcium channel were satisfied for further animal assay using disease model.
- Lee, Hyung Kook,Lee, Yun Suk,Roh, Eun Joo,Rhim, Hyewhon,Lee, Jae Yeol,Shin, Kye Jung
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scheme or table
p. 4424 - 4427
(2009/04/06)
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- Synthesis of 1-benzothiepine and 1-benzazepine derivatives as orally active CCR5 antagonists
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Quaternary ammonium benzocycloheptene compound 1 has previously been reported as a clinical candidate for an injectable CCR5 antagonist. In order to develop an orally active CCR5 antagonist, derivatives of tertiary amine benzocycloheptene 2, the chemical precursor to 1, were investigated. The benzocycloheptene ring was converted to benzothiepine and benzazepine rings and it was found that these changes could enhance the potency of tertiary amine derivatives. In particular, the 1-benzothiepine-1,1-dioxide 11b and the N-methyl-1-benzazepine 18 showed increased activity and good preliminary pharmacokinetic properties. The synthesis of 1-benzothiepine and 1-benzazepine derivatives and their activity are described.
- Aramaki, Yoshio,Seto, Masaki,Okawa, Tomohiro,Oda, Tsuneo,Kanzaki, Naoyuki,Shiraishi, Mitsuru
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p. 254 - 258
(2007/10/03)
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- Novel Asp32-replacement tetrapeptide analogues as potent and selective CCK-A agonists
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A series of novel CCK tetrapeptide analogues of the general formula Boc- Trp-Lys(Tac)-N(R)-(CH2)(n)CON(R')Phe-NH2 (Tac = o-tolylaminocarbonyl), where R,R' = H or Me and n = 1-5, have been synthesized and tested. These analogues, which lack an acidic residue at the penultimate position, demonstrated surprisingly high CCK-A receptor affinity and selectivity. The effect of N-methylation pattern on CCK-A receptor affinity showed consistent trends for analogues in which n = 1, 2, or 3, with the di-N-methylated analogues having the highest affinity in each case. However, none of these analogues had full agonist activity, as measured by percent maximal PI hydrolysis. Two conformationally constrained analogues also demonstrated high CCK-A receptor affinity and selectivity, as well as nearly maximal agonist activity. In addition, one of these conformationally-constrained analogues demonstrated anorectic activity in rats.
- Elliott,Kopecka,Tufano,Shue,Gauri,Lin -,Bianchi,Miller,Witte,Stashko,Asin,Nikkel,Bednarz,Nadzan
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p. 1562 - 1568
(2007/10/02)
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