{"id":354,"date":"2014-06-21T01:05:48","date_gmt":"2014-06-21T01:05:48","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=354"},"modified":"2014-08-31T16:23:36","modified_gmt":"2014-08-31T20:23:36","slug":"the-rapid-rise-of-sulfonamide-diversity","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2014\/06\/21\/354\/the-rapid-rise-of-sulfonamide-diversity\/","title":{"rendered":"The Rapid Rise of Sulfonamide Diversity"},"content":{"rendered":"

\"Prontosil\"<\/a>Shortly after Domagk and H\u00f6rlein announced their discovery of the antibacterial properties of the dye sulfamidochrysoidine (Prontosil) in 1935, numerous\u00a0chemical companies\u00a0set out to\u00a0modify the chemical structure. \u00a0They soon recognized the sulfa component as the true antibacterial and produced an incredible number of derivatives (more than 5000 different compounds!!) by 1945.[1, 2] \u00a0This effort was undoubtedly\u00a0helped by the fact that Bayer had not\u00a0patented the antibacterial sulfa pharmacophore but the dye part of the molecule instead. \u00a0Big mistake!<\/p>\n

In those early days drugs were tested without much\u00a0regulatory\u00a0oversight. Soon, impressive efficacy data were collected demonstrating clinical benefits\u00a0in various tissue infectious caused by staphylococci and streptococci. While many trials were small and uncontrolled,\u00a0some older studies provided\u00a0important insights. For instance, the skin infection studies conducted by\u00a0Snodgrass [3] are still often cited; indeed, they served as\u00a0scientific basis for the\u00a0most recent FDA guidelines for\u00a0ABSSSI trials, providing efficacy comparisons to placebo and helping define non-inferiority margins.[4]<\/p>\n

There were some early warnings about drug safety and tolerability. \u00a0Besides rashes and other allergic reaction, the practice of instillation, irrigation and insufflation of some very alkaline sulfa compounds into the nose, nasal sinuses and bronchial tree resulted in sloughing of epithelial layers and tissue necrosis.[2] \u00a0These AEs did not cause undue concerns as the treatment benefits were\u00a0just so compelling.<\/p>\n

 <\/p>\n

\n

1. \u00a0Greenwood. \u00a0Antimicrobial Drugs. \u00a0Chronicle of a Twentieth Century Medical Triumph. \u00a0Oxford University Press 2008
\n2. \u00a0Northey. The Sulphonamides and Allied Compounds. \u00a0Reinhold Pub. Corp.<\/span>,<\/span>1948
\n3. \u00a0Snodgrass.\u00a0\u00a0BMJ, 2:101; 1937 \u00a0and\u00a0BMJ, 2:1159; 1937
\n4. FDA: \u00a0Guidance for Industry. \u00a0Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment. \u00a02013; http:\/\/www.fda.gov\/downloads\/Drugs\/…\/Guidances\/ucm071185.pdf<\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Shortly after Domagk and H\u00f6rlein announced their discovery of the antibacterial properties of the dye sulfamidochrysoidine (Prontosil) in 1935, numerous\u00a0chemical companies\u00a0set out to\u00a0modify the chemical structure. \u00a0They soon recognized the sulfa component as the true antibacterial and produced an incredible number of derivatives (more than 5000 different compounds!!) by 1945.[1, Continue reading The Rapid Rise of Sulfonamide Diversity<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[140],"tags":[81,152,5,99,153,158,155,9,154,156,141,157],"class_list":["post-354","post","type-post","status-publish","format-standard","hentry","category-interesting_facts","tag-absssi","tag-domagk","tag-fda","tag-fda-guidance","tag-non-inferiority","tag-non-inferiority-margins","tag-prontosil-patent","tag-safety","tag-snodgrass","tag-sulfachrysoidine","tag-sulfonamide","tag-uncontrolled-trials"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-5I","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":2774,"url":"https:\/\/allphasepharma.com\/dir\/2016\/10\/06\/2774\/sulfonamides-revisited-with-an-emphasis-on-dapsone\/","url_meta":{"origin":354,"position":0},"title":"Sulfonamides Revisited, With an Emphasis on Dapsone","author":"Harald","date":"October 6, 2016","format":false,"excerpt":"The sulfonamide moiety is a remarkable structure giving rise to diverse drugs in arious therapeutic areas such as antibiotics, antidiabetics, diuretics and anti-inflammatory agents. In regards to antibiotics, sulfonamides\u00a0are in common use as antifungals (P. jiroveci), antiparasitics (toxoplasmosis, cyclospora, isospora, malaria) antibacterials (including against nocardia and certain ones causing STDs)\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"deutsche-med-wschr-1935","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/Deutsche-Med-Wschr-1935.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/Deutsche-Med-Wschr-1935.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/Deutsche-Med-Wschr-1935.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":344,"url":"https:\/\/allphasepharma.com\/dir\/2014\/06\/19\/344\/the-amazing-sulfonamides\/","url_meta":{"origin":354,"position":1},"title":"The Amazing Sulfonamides","author":"Harald","date":"June 19, 2014","format":false,"excerpt":"Sulfonamides really cover more infectious territory than most other antibiotics. Besides the more common bacterial species, they are\u00a0active\u00a0against many 'special' pathogens, like S. maltophilia,\u00a0P. jiroveci, Listeria, Nocardia,, C. burneti (Q-fever), and T. whipplei (Whipple's disease). Not to forget their\u00a0use in malaria, toxoplasmosis, \u00a0melioidosis, cyclospora, and atypical mycobacterial infections. Then there\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":1254,"url":"https:\/\/allphasepharma.com\/dir\/2015\/02\/02\/1254\/a-go-no-go-decision-delafloxacin-stumbles-in-gonorrhea-study\/","url_meta":{"origin":354,"position":2},"title":"A GO \/ NO GO decision:\u00a0 Delafloxacin Stumbles in Gonorrhea Study","author":"Harald","date":"February 2, 2015","format":false,"excerpt":"The treatment history of N. gonorrhoeae makes for fascinating reading.\u00a0 This organism has always been able to keep the upper hand in the war of bug versus drug.\u00a0 Once susceptible to sulfa drugs, to penicillin, tetracyclines and fluoroquinolones, it sequentially become resistant in the matter of a decade to every\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"mic-2","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/02\/mic-2.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":2129,"url":"https:\/\/allphasepharma.com\/dir\/2015\/11\/14\/2129\/ibuprofen-for-uuti-interesting-pilot-trial-but-more-to-come-soon\/","url_meta":{"origin":354,"position":3},"title":"Ibuprofen For uUTI: Interesting Pilot Trial But More to Come Soon","author":"Harald","date":"November 14, 2015","format":false,"excerpt":"At the recent AMDAC, the frequent mention of an unusual uUTI study caught my attention.\u00a0 In their review of placebo-controlled trials, FDA mentioned a study comparing ciprofloxacin with Ibuprofen (Motrin), an NSAID drug without any antibacterial activity[1].\u00a0 By the outcome of total symptom relief, there was no difference. Obviously, there\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"uUTI study slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/uUTI-study-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/uUTI-study-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/uUTI-study-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":4723,"url":"https:\/\/allphasepharma.com\/dir\/2025\/07\/13\/4723\/microbiological-response-as-primary-efficacy-endpoint-for-antibacterials\/","url_meta":{"origin":354,"position":4},"title":"Microbiological Response as Primary Efficacy Endpoint for Antibacterials","author":"Harald","date":"July 13, 2025","format":false,"excerpt":"We have often mentioned the central importance of microbiological response as an endpoint in trials of antibacterials. This is contrary to other therapeutic areas, in which the etiology is less understood and where surrogate markers are needed. In bacterial infectious diseases we have the luxury of knowing exactly what causes\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/HR_SLIDER-MICROBIOLOGY-STUPID.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/HR_SLIDER-MICROBIOLOGY-STUPID.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/HR_SLIDER-MICROBIOLOGY-STUPID.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":4303,"url":"https:\/\/allphasepharma.com\/dir\/2025\/05\/05\/4303\/sulopenem-uuti-does-it-suffice\/","url_meta":{"origin":354,"position":5},"title":"Sulopenem uUTI – Does It Suffice?","author":"Harald","date":"May 5, 2025","format":false,"excerpt":"Sulopenem \/ ORLYNVAH approved for uUTI When Iterum, a Pfizer spin-off of sorts, took over sulopenem development in 2015, there was still hope for approvals of this drug in multiple indications such as uUTI, cUTI, cIAI and even CABP.\u00a0 Ten years later and after an FDA rejection CRL in 2021,\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/05\/Sulopenem-in-uUTI-SLIDER.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/05\/Sulopenem-in-uUTI-SLIDER.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/05\/Sulopenem-in-uUTI-SLIDER.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/354","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/comments?post=354"}],"version-history":[{"count":11,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/354\/revisions"}],"predecessor-version":[{"id":821,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/354\/revisions\/821"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=354"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=354"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=354"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}