AHA001

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: AHA001
• 英文别名: (4R,5S,6S,7R)-1,3-dibenzyl-5,6-dihydroxy-4,7-bis(phenoxymethyl)-1,3-diazepan-2-one
• 化学式: C₃₃H₃₄N₂O₅
• 分子量: 538.643
• InChiKey: SQBOSZXDOHQFAA-ZRTHHSRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,5-diazido-3,4-O-isopropylidene-1,6-di-O-phenyl-2,5-dideoxy-D-iditol 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 9.25h， 生成 AHA001
  参考文献：
  名称：

  Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities

  摘要：

  Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.

  DOI：

  10.1021/jm960728j

文献信息

• Advanced drug development and manufacturing
  申请人：Birnbaum Eva R.

  公开号：US20080220441A1

  公开（公告）日：2008-09-11

  X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, and for drug manufacturing.
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• [DE] NEUE CHEMISCHE VERBINDUNGEN, DEREN HERSTELLUNG UND DEREN VERWENDUNG<br/>[EN] NOVEL CHEMICAL COMPOUNDS, PRODUCTION THEREOF, AND USE THEREOF<br/>[FR] NOUVEAUX COMPOSES CHIMIQUES, LEUR FABRICATION ET UTILISATION
  申请人：UNIV LEIPZIG

  公开号：WO2008145733A2

  公开（公告）日：2008-12-04

  [EN] The patent application relates to chemical compounds with a basic structure selected from salicylic acid, acetylsalicylic acid, APHS (o-acetoxyphenylhept-2-inylsulfid), salen ligands, diflunisal, salsalate, benorylate, phenylalkanylcarbon acids (particularly fenoprofen, ibuprofen, ketoprofen, flurbiprofen, naproxen, tolmetin, sulindac, indomethacin, diclofenac, carprofen, etodolac, ketorolac), oxicam inhibitors (particularly Tenoxicam, Prioxicam, Meloxicam), anthranilic acids: (particularly mefenamic acid, meclofenamic acid), sulfonamides (particularly celecoxib and valdecoxib), methyl sulphones (particularly rofecoxib, etoricoxib, DuP697 (CAS 88149-94-4), NS398 (CAS 123653-11-2), flosulide (CGP28238), nimesulide, diaryl heterocyclene (particularly sodium parecoxib), propanamides (particularly parecoxib), butanzone (particularly phenylbutazone, oxyphenylbutazone), paracetamol, phenacetin, phenazone, dipyrone, amidopyrine, and esters and acid amides of the compounds mentioned, methotrexate, Br-R99219, trimethoprim, tipranavir, indinavir, ritonavir, JH-174 and NMB-006, thyronin, thyroxine and triiodothyronine, butylscopolamine bromide, clonidine, duloxetine, fenoterol, losartan, oxazepam, lorazepam, salbutamol, tiotropium bromide, atorvastatin, simvastatin, olanzapine, amlodipine, clopidogrel, sertraline, resveratrol, 1-Phenylpropan-2-amine and N-Methy-1-phenylpropan-2-amine, ephedrine, and the pharmaceutically acceptable salts, hydrates, solvents, and metal complexes of the compounds mentioned, wherein the basic structure is modified such that it comprises at least one cluster, preferably a cluster containing borate. The invention further relates to a method for the production and use thereof in pharmaceuticals, as catalysts, and as materials.
  [FR] La demande de brevet concerne des composés chimiques avec une structure fondamentale choisie parmi les éléments suivants: acide salicylique, acide acétylsalicylique, APHS (o-acetoxyphenylhept-2-inylsulfide), ligands salen, diflunisal, salsalate, bénorilate, acides carboxyliques de phénylalcanyle (notamment fénoprofène, ibuprofène, kétoprofène, flurbiprofène, naproxène, tolmétine, sulindac, indométhacine, diclofénac, carprofène, étodolac, kétorolac), inhibiteurs d'oxicam (notamment ténoxicam, prioxicam, méloxicam), acides anthraniliques (notamment acide de méfénamine, aminoacide de méclofène), sulfonamides (notamment célécoxib et valdecoxib), méthylsulfones (notamment rofecoxib, étoricoxib, DuP697 (CAS 88149-94-4), NS398 (CAS 123653-11-2), flosulide (CGP28238), nimesulide, hétérocycles de diaryl (notamment parecoxib sodium), amides de propane (notamment parecoxib), butazones (notamment phényl butazone, oxyphényl butazone), paracétamole, phénacétine, phénazone, dipyrone, amidopyrine, esters et amides d'acide des composés indiqués, methotrexat, Br-WR99219, triméthoprime, tipranavir, indinavir, ritonavir, JH-174 et NMB-006, thyronine, thyroxine et triiodothyronine, bromure de butylscopolamine, clonidine, duloxétine, fénotérol, losartan, oxazépam, lorazépam, salbutamol, bromure de tiotropium, atorvastatine, simvastatine, olanzapine, amlodipine, clopidogrel, sertraline, résvératrol, 1-phénylpropane-2-amine et N-méthy-1-phénylpropane-2-amine, éphédrine ainsi que les sels, hydrates, solvates et complexes métalliques pharmaceutiquement compatibles des composés indiqués, la structure fondamentale étant modifiée de manière à ce qu'elle comprenne au moins un cluster, de préférence un cluster contenant du bore. L'invention porte également sur un procédé de fabrication ainsi que sur l'utilisation de ces composés en pharmacie, pour la catalyse et en tant que matériaux.
  [DE] Die Patentanmeldung betrifft chemische Verbindungenmiteiner Grundstruktur ausgewählt aus Salicylsäure, Acetylsalicylsäure, APHS (o-Acetoxyphenylhept-2-inylsulfid), Salenliganden, Diflunisal, Salsalat, Benorylat, Phenylalkanylcarbonsäuren (insbesondere Fenoprofen, Ibuprofen, Ketoprofen, Flurbiprofen, Naproxen, Tolmetin, Sulindac, Indomethacin, Diclofenac, Carprofen, Etodolac, Ketorolac), Oxicaminhibitoren (insbesondere Tenoxicam, Prioxicam, Meloxicam), Anthranil-Säuren: (insbesondere Mefenaminsäure, Meclofenaminsäure) Sulfonamiden (insbesondere Celecoxib und Valdecoxib), Methylsulfonen (insbesondere, Rofecoxib, Etoricoxib, DuP697 (CAS 88149-94-4), NS398 (CAS 123653-11-2), Flosulid (CGP28238), Nimesulid, Diarylheterocyclen (insbesondere Natriumparecoxib), Propanamiden (insbesondere Parecoxib), Butazone (insbesondere Phenylbutazon, Oxyphenylbutazon), Paracetamol,Phenacetin, Phenazon, Dipyron, Amidopyrin, sowie Ester und Säureamide der genannten Verbindungen,Methotrexat, Br-WR99219,Trimethoprim,Tipranavir, Indinavir, Ritonavir, JH-174 und NMB-006, Thyronin, Thyroxin und Triiodothyronin, Butylscopolaminiumbromid, Clonidin, Duloxetin, Fenoterol, Losartan, Oxazepam, Lorazepam, Salbutamol,Thiotropiumbromid, Atorvastatin, Simvastatin, Olanzapin, Amlodipin, Clopidogrel, Sertralin, Resveratrol, 1-Phenylpropan-2-amin und N-Methy-1-phenylpropan-2-amin, Ephedrin sowie den pharmazeutisch verträglichen Salzen, Hydraten, Solvaten und Metallkomplexen der genannten Verbindungen, wobei die Grundstruktur dahingehend modifiziert ist, dass sie mindestens einen Cluster, vorzugsweise Bor-haltigen Cluster, enthält, Verfahren zur Herstellung, sowiederen Verwendung in der Pharmazie,Katalyse und als Materialien.
• Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities
  作者：Johan Hultén、Nicholas M. Bonham、Ulrika Nillroth、Tomas Hansson、Guido Zuccarello、Abderrahim Bouzide、Johan Åqvist、Björn Classon、U. Helena Danielson、Anders Karlén、Ingemar Kvarnström、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm960728j

  日期：1997.3.1

  Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.