{"entity": "journal", "iuid": "ee3b8ba5023c451894f263b90c954942", "timestamp": "2026-07-12T08:26:36.081Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/ACS%20Med%20Chem%20Lett.json"}, "display": {"href": "https://publications.scilifelab.se/journal/ACS%20Med%20Chem%20Lett"}}, "title": "ACS Med Chem Lett", "issn": "1948-5875", "issn-l": "1948-5875", "publications_count": 6, "publications": [{"entity": "publication", "iuid": "e68983c84bbc41d8a88758e197b58a33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e68983c84bbc41d8a88758e197b58a33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e68983c84bbc41d8a88758e197b58a33"}}, "title": "Potent Neuronal Nicotinamide Adenine Dinucleotide-Boosting Tetrahydroquinoxalines: Structure-Activity Relationships and Early Drug Metabolism and Pharmacokinetics Evaluation.", "authors": [{"family": "Cu\u0159\u00ednov\u00e1", "given": "Petra", "initials": "P", "orcid": "0000-0001-8264-7032", "researcher": {"href": "https://publications.scilifelab.se/researcher/f196559d7e954e448879878768bc213e.json"}}, {"family": "J\u00f6e", "given": "Melissa", "initials": "M"}, {"family": "Cesar", "given": "Filip", "initials": "F"}, {"family": "Nicol", "given": "Alan", "initials": "A"}, {"family": "Schwan", "given": "Kristi\u00e1n", "initials": "K"}, {"family": "Kohout", "given": "Michal", "initials": "M", "orcid": "0000-0003-1447-4453", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4f2547f153b43d79c0364607cd518c6.json"}}, {"family": "Varrichio", "given": "Carmine", "initials": "C"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-8113-0653", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51.json"}}, {"family": "J\u00f3hannesson", "given": "Gauti", "initials": "G"}, {"family": "Eigner", "given": "V\u00e1clav", "initials": "V"}, {"family": "Tribble", "given": "James R", "initials": "JR"}, {"family": "Brancale", "given": "Andrea", "initials": "A", "orcid": "0000-0002-9728-3419", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa54df57e794ee3a2b98108bd694277.json"}}, {"family": "Williams", "given": "Pete A", "initials": "PA", "orcid": "0000-0001-6194-8397", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b4d7eb42dcd4c489a97198a043b3806.json"}}], "type": "journal article", "published": "2026-04-09", "journal": {"title": "ACS Med Chem Lett", "issn": "1948-5875", "volume": "17", "issue": "4", "pages": "916-924", "issn-l": "1948-5875"}, "abstract": "We designed and synthesized a series of novel 1,2,3,4-tetrahydroquinoxaline derivatives and evaluated their ability to increase nicotinamide adenine dinucleotide (NAD) levels in primary cortical neurons. Several compounds demonstrated nanomolar potency and enabled the establishment of clear structure-activity relationships (SAR), highlighting key substituents required for activity. Qualitative 3DSAR analysis further identified favorable steric, electrostatic, and hydrophobic features associated with NAD enhancement. Selected lead compounds were assessed for in vitro drug metabolism and pharmacokinetics (DMPK) properties, showing good cell permeability and species-dependent metabolic stability in liver microsomes, with improved stability in human systems compared with rodent systems. These findings identify tetrahydroquinoxalines as a promising class of neuronal NAD-boosting agents and provide a strong foundation for further optimization toward neuroprotective drug candidates.", "doi": "10.1021/acsmedchemlett.6c00058", "pmid": "41982735", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13071616"}], "notes": [], "created": "2026-05-14T20:21:50.854Z", "modified": "2026-05-14T20:21:51.275Z"}, {"entity": "publication", "iuid": "3355c650475e4ce5881d5835cff6729e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3355c650475e4ce5881d5835cff6729e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3355c650475e4ce5881d5835cff6729e"}}, "title": "NMR Backbone Assignment of VIM-2 and Identification of the Active Enantiomer of a Potential Inhibitor", "authors": [{"family": "Wieske", "given": "Lianne H E", "initials": "LHE", "orcid": "0000-0003-4617-7605", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ee9a8547a194235a4d32170996b53e9.json"}}, {"family": "Bogaerts", "given": "Jonathan", "initials": "J", "orcid": "0000-0001-8089-7759", "researcher": {"href": "https://publications.scilifelab.se/researcher/921da51be41e4b41b3b3499ae7cc61d6.json"}}, {"family": "Leding", "given": "Albin A M", "initials": "AAM", "orcid": "0000-0003-1071-6929", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d765f3a2bcd4957ab279471c1dd4fa9.json"}}, {"family": "Wilcox", "given": "Scott", "initials": "S"}, {"family": "Andersson Rasmussen", "given": "Anna", "initials": "A"}, {"family": "Leszczak", "given": "Kinga", "initials": "K"}, {"family": "Turunen", "given": "Lotta", "initials": "L"}, {"family": "Herrebout", "given": "Wouter A", "initials": "WA", "orcid": "0000-0002-3167-8944", "researcher": {"href": "https://publications.scilifelab.se/researcher/bba405b9bce14713a0635a6999f7666a.json"}}, {"family": "Hubert", "given": "Madlen", "initials": "M"}, {"family": "Bayer", "given": "Annette", "initials": "A", "orcid": "0000-0003-3481-200X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e921a3a52ec047cdae2961e37a4aac46.json"}}, {"family": "Erd\u00e9lyi", "given": "M\u00e1t\u00e9", "initials": "M", "orcid": "0000-0003-0359-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/f772b571449e417ca6fda2eee361a0c3.json"}}], "type": "journal-article", "published": "2022-02-10", "journal": {"title": "ACS Med Chem Lett", "issn": "1948-5875", "volume": "13", "issue": "2", "pages": "257-261", "issn-l": "1948-5875"}, "abstract": null, "doi": "10.1021/acsmedchemlett.1c00635", "pmid": null, "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2022-04-25T12:00:22.113Z", "modified": "2025-10-17T13:03:55.008Z"}, {"entity": "publication", "iuid": "5f4b3a7c780f4555b649b7dc7c33670e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5f4b3a7c780f4555b649b7dc7c33670e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5f4b3a7c780f4555b649b7dc7c33670e"}}, "title": "Cell Permeability of Isomeric Macrocycles: Predictions and NMR Studies.", "authors": [{"family": "Begnini", "given": "Fabio", "initials": "F"}, {"family": "Poongavanam", "given": "Vasanthanathan", "initials": "V", "orcid": "0000-0002-8880-9247", "researcher": {"href": "https://publications.scilifelab.se/researcher/d037f230665c490dada0a50ecc8c106f.json"}}, {"family": "Atilaw", "given": "Yoseph", "initials": "Y"}, {"family": "Erdelyi", "given": "Mate", "initials": "M", "orcid": "0000-0003-0359-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/f772b571449e417ca6fda2eee361a0c3.json"}}, {"family": "Schiesser", "given": "Stefan", "initials": "S", "orcid": "0000-0002-8668-2844", "researcher": {"href": "https://publications.scilifelab.se/researcher/c173ef3958eb49dea045b6962483b494.json"}}, {"family": "Kihlberg", "given": "Jan", "initials": "J", "orcid": "0000-0002-4205-6040", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9805d4f39cc48f79a6e6ba076917021.json"}}], "type": "journal article", "published": "2021-06-10", "journal": {"title": "ACS Med Chem Lett", "issn": "1948-5875", "volume": "12", "issue": "6", "pages": "983-990", "issn-l": "1948-5875"}, "abstract": "Conformation-dependent 3D descriptors have been shown to provide better predictions of the physicochemical properties of macrocycles than 2D descriptors. However, the computational identification of relevant conformations for macrocycles is nontrivial. Herein, we report that the Caco-2 cell permeability difference between a pair of diastereomeric macrocycles correlated with their solvent accessible 3D polar surface area and radius of gyration. The descriptors were calculated from the macrocycles' solution-phase conformational ensembles and independently from ensembles obtained by conformational sampling. Calculation of the two descriptors for three other stereo- and regioisomeric macrocycles also allowed the correct ranking of their cell permeability. Methods for conformational sampling may thus allow ranking of passive permeability for moderately flexible macrocycles, thereby contributing to the prioritization of macrocycles for synthesis in lead optimization.", "doi": "10.1021/acsmedchemlett.1c00126", "pmid": "34136079", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8201747"}], "notes": [], "created": "2021-07-02T14:05:55.552Z", "modified": "2025-10-17T13:03:55.774Z"}, {"entity": "publication", "iuid": "3ffc1a6f6e384d9fb4f56feca73408f6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3ffc1a6f6e384d9fb4f56feca73408f6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3ffc1a6f6e384d9fb4f56feca73408f6"}}, "title": "N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity.", "authors": [{"family": "Thota", "given": "Niranjan", "initials": "N"}, {"family": "Makam", "given": "Parameshwar", "initials": "P"}, {"family": "Rajbongshi", "given": "Kamal K", "initials": "KK"}, {"family": "Nagiah", "given": "Savania", "initials": "S"}, {"family": "Abdul", "given": "Naeem Sheik", "initials": "NS"}, {"family": "Chuturgoon", "given": "Anil A", "initials": "AA"}, {"family": "Kaushik", "given": "Amit", "initials": "A"}, {"family": "Lamichhane", "given": "Gyanu", "initials": "G"}, {"family": "Somboro", "given": "Anou M", "initials": "AM"}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG"}, {"family": "Govender", "given": "Thavendran", "initials": "T"}, {"family": "Naicker", "given": "Tricia", "initials": "T"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}], "type": "journal article", "published": "2019-10-10", "journal": {"title": "ACS Med Chem Lett", "issn": "1948-5875", "volume": "10", "issue": "10", "pages": "1457-1461", "issn-l": "1948-5875"}, "abstract": "Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram - Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4-8 \u03bcg/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC50 = 15 \u03bcg/mL; compound 15 IC50 = 65 \u03bcg/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design.", "doi": "10.1021/acsmedchemlett.9b00285", "pmid": "31620233", "labels": {"Drug Discovery and Development": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC6792286"}], "notes": [], "created": "2020-01-08T11:29:23.555Z", "modified": "2025-10-17T13:05:08.170Z"}, {"entity": "publication", "iuid": "f219b8ba9c774978a91abe62e1bd379b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f219b8ba9c774978a91abe62e1bd379b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f219b8ba9c774978a91abe62e1bd379b"}}, "title": "Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel substance p 1-7 analogues.", "authors": [{"family": "Fransson", "given": "Rebecca", "initials": "R"}, {"family": "Nordvall", "given": "Gunnar", "initials": "G"}, {"family": "Bylund", "given": "Johan", "initials": "J"}, {"family": "Carlsson-Jonsson", "given": "Anna", "initials": "A"}, {"family": "Kratz", "given": "Jadel M", "initials": "JM"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}, {"family": "Sandstr\u00f6m", "given": "Anja", "initials": "A"}], "type": "journal article", "published": "2014-12-11", "journal": {"volume": "5", "issn": "1948-5875", "issue": "12", "pages": "1272-1277", "title": "ACS Med Chem Lett", "issn-l": "1948-5875"}, "abstract": "The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a bioisosteric replacement for the original primary amide.", "doi": "10.1021/ml5002954", "pmid": "25516784", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC4265825"}], "notes": [], "created": "2017-10-31T12:47:52.738Z", "modified": "2025-10-17T13:04:29.863Z"}, {"entity": "publication", "iuid": "1d7c8ede238a4108b461af15313d4c25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d7c8ede238a4108b461af15313d4c25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d7c8ede238a4108b461af15313d4c25"}}, "title": "Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2-P1' Region.", "authors": [{"family": "Lampa", "given": "Anna K", "initials": "AK"}, {"family": "Bergman", "given": "Sara M", "initials": "SM"}, {"family": "Gustafsson", "given": "Sofia S", "initials": "SS"}, {"family": "Alogheli", "given": "Hiba", "initials": "H"}, {"family": "Akerblom", "given": "Eva B", "initials": "EB"}, {"family": "Lindeberg", "given": "Gunnar G", "initials": "GG"}, {"family": "Svensson", "given": "Richard M", "initials": "RM"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Danielson", "given": "U Helena", "initials": "UH"}, {"family": "Karl\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Sandstr\u00f6m", "given": "Anja", "initials": "A"}], "type": "journal article", "published": "2014-03-13", "journal": {"volume": "5", "issn": "1948-5875", "issue": "3", "pages": "249-254", "title": "ACS Med Chem Lett", "issn-l": "1948-5875"}, "abstract": "Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.", "doi": "10.1021/ml400217r", "pmid": "24900813", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC4027635"}], "notes": "Uppsala Drug Optimization and Pharmaceutical Profiling (UDOPP)\r\nADME of Therapeutics (UDOPP)", "created": "2017-05-04T14:56:46.200Z", "modified": "2025-10-17T13:04:30.141Z"}], "created": "2017-05-09T09:11:59.369Z", "modified": "2020-11-27T13:14:08.451Z"}