{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:35:24Z","timestamp":1787927724422,"version":"build-2784847793"},"reference-count":68,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Despite advancements in molecular design rules and understanding biochemical processes, the field of drug design and discovery seeks to minimize the number and duration of synthesis\u2010testing cycles to convert lead compounds into drug candidates. A promising strategy involves gaining insightful understanding of key heteroatoms such as oxygen and nitrogen. This work presents a comprehensive analysis of oxygen atoms in approved drugs, aiming to streamline drug design and discovery efforts. The study examines the frequency, distribution, prevalence, and diversity of oxygen atoms in a dataset of 2049 small molecules approved by the FDA and other agencies. The analysis focuses on various types of oxygen atoms, including sp<jats:sup>3<\/jats:sup>, sp<jats:sup>2<\/jats:sup>\u2010hybridized, ring, and nonring. In general, existence of sp<jats:sup>3<\/jats:sup>\u2010O slightly outperforms sp<jats:sup>2<\/jats:sup>\u2010O, which is associated with balancing various factors such as flexibility, solubility, stability, and pharmacokinetics, in addition to activity and selectivity. In approved drugs, majority of oxygen atoms are present within 4\u2009\u00c5 from the COM of the molecule. This analysis offers valuable understanding of oxygen distribution, which could be used during the multiparameter optimization process, facilitating the transformation of a hit\/lead compound into a potential drug candidate.<\/jats:p>","DOI":"10.1111\/cbdd.70060","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T10:35:52Z","timestamp":1738838152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Analyzing Oxygen Atom Distribution in FDA\u2010Approved Drugs to Enhance Drug Discovery Strategies"],"prefix":"10.1111","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9300-4147","authenticated-orcid":false,"given":"Vijay H.","family":"Masand","sequence":"first","affiliation":[{"name":"Department of Chemistry Vidya Bharati Mahavidyalaya  Amravati Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-5016","authenticated-orcid":false,"given":"Meghshyam K.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Chemistry Dr. Babasaheb Ambedkar Marathwada University, Sub\u2010Campus  Dharashiv Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami A.","family":"Al\u2010Hussain","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Samad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Tishk International University  Erbil Kurdistan Region Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Rastija","sequence":"additional","affiliation":[{"name":"Department of Agroecology and Environmental Protection, Faculty of Agrobiotechnical Sciences Osijek Josip Juraj Strossmayer University of Osijek  Osijek Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul D.","family":"Jawarkar","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Dr. Rajendra Gode Institute of Pharmacy  Amravati Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav S.","family":"Masand","sequence":"additional","affiliation":[{"name":"Dr. D. Y. Patil Unitech Society's Dr. D. Y. Patil Institute of Technology  Pune Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakhi G.","family":"Gawali","sequence":"additional","affiliation":[{"name":"Department of Chemistry D.B.F. Dayanand College of Arts &amp; Science  Solapur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdi E. A.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.2.4.554"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12260"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102377\u20109\u2010s1\u2010s3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.075929"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.7b02914"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.237"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1sc03563k"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c02015"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012741107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trechm.2019.04.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00717"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00876"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801076-1.00010-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2017.1264385"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2014.08.013"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01286"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105274"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr777"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/cc9800071"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.26455"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01855"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2568"},{"key":"e_1_2_9_24_1","volume-title":"Essentials of Molecular Pharmacology; Background for Drug Design","author":"Korolkovas A.","year":"1970"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100087s"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm801331y"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjaceaccp\/mkr018"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2004.11.007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0169\u2010409x(00)00129\u20100"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901241e"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2023.2266990"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2020.129597"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemolab.2017.08.003"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.197"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578\u2010021\u201000394\u2010w"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00915"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20103\u201033"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3078"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01807"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118681121"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct9000922"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1088\/0256\u2010307x\/27\/8\/084702"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.5402\/2012\/195727"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2019.02.004"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00473"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2017.1356820"},{"key":"e_1_2_9_47_1","volume-title":"The Organic Chemistry of Drug Design and Drug Action","author":"Silverman R. B.","year":"2014"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006\u20102952(02)01068\u20107"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501105n"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20102952(92)90333\u2010e"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.02.002"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm4017625"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.12.023"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002426"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.88026"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0sc05788f"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.8b00415"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501100b"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2012.648612"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200504p"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010020\u201005361\u20102"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4609"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2014.1289"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02643"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1298"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15060745"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201077033\u2010x"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22020279"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:59:57Z","timestamp":1741744797000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.70060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":68,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/cbdd.70060"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.70060","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70060"}}