403:
29:
479:
946:
While little information is available regarding the regulatory and commercialization history of
Dalfopristin alone, Synercid (quinupristin/dalfopristin), made by Rhone-Poulenc Rorer Pharmaceuticals, was approved in 1999 as an IV injectable for the treatment of vancomycin resistant Enterococcus
521:
InChI=1S/C34H50N4O9S/c1-7-37(8-2)16-17-48(44,45)28-13-15-38-31(28)34(43)47-32(22(3)4)24(6)11-12-29(41)35-14-9-10-23(5)18-25(39)19-26(40)20-30-36-27(21-46-30)33(38)42/h9-12,18,21-22,24-25,28,31-32,39H,7-8,13-17,19-20H2,1-6H3,(H,35,41)/b10-9+,12-11+,23-18+/t24-,25-,28-,31-,32-/m1/s1
898:
offers the benefit of requiring multiple points of mutation targeting both dalfopristin and quinupristin components to confer drug resistance. Comparatively, only 2-5% of staphylococcal isolates collected in France show resistance to a related streptogramin,
877:
Streptogramin resistance is mediated through enzymatic drug inactivation, efflux or active transport of drug out of the cell, and most commonly, conformational alterations in ribosomal target binding sites. Enzymatic drug inactivation may occur in
865:. Initial dalfopristin binding results in a conformational change of the ribosome, allowing for increased binding by quinupristin. A stable drug-ribosome complex is created when the two drugs are used together. This complex inhibits
886:
species through production of dalfopristin-inactivating acetyltransferase or quinupristin-inactivating hydrolase. Efflux or active transport of the drug may occur in coagulase-negative staphylococci and
73:
537:
41:
493:
869:
through prevention of peptide-chain formation and blocking the extrusion of newly formed peptide chains. In many cases, this leads to bacterial cell death.
947:
faecium and complicated skin and skin structure infections. Dalfopristin can be purchased alone on the internet from various chemical manufacturers as a
1120:
1043:
Barrière JC, Berthaud N, Beyer D, Dutka-Malen S, Paris JM, Desnottes JF (April 1998). "Recent developments in streptogramin research".
850:
513:
911:
Both dalfopristin and quinupristin are extensively hepatically metabolized, excreted from the feces, and serve as an inhibitor of
853:, in vitro studies have not demonstrated bactericidal activity against all strains and species of common gram-positive bacteria.
1135:
148:
94:
666:
of 2-diethylaminoethanethiol on the conjugated double bond of the dehydroproline ring . The first method found was using
302:
382:
686:
in a 2-phase medium produces an improved yield, and is therefore the method of choice for large scale production.
935:
920:
895:
842:
690:
581:
577:
891:. Constitutive ribosome modification has been seen in staphylococci with resistance seen in quinupristin only.
988:
834:
371:
915:(CYP) 3A4 enzyme pathway. Caution should be taken with concommitent use with drugs metabolized by the
1125:
888:
127:
398:
217:
28:
931:
1130:
1096:
1052:
1022:
866:
679:
671:
291:
109:
351:
1088:
1014:
789:
683:
667:
663:
585:
419:
226:
119:
311:
1079:
Allington DR, Rivey MP (January 2001). "Quinupristin/dalfopristin: a therapeutic review".
1005:
Allington DR, Rivey MP (January 2001). "Quinupristin/dalfopristin: a therapeutic review".
912:
719:
693:
is achieved through purifying cocrystallization of the quinupristin and dalfopristin from
573:
501:
CCN(CC)CCS(=O)(=O)1CCN21C(=O)O((/C=C/C(=O)NC/C=C/C(=C/(CC(=O)CC3=NC(=CO3)C2=O)O)/C)C)C(C)C
402:
51:
879:
846:
838:
826:
659:
601:
188:)-26-sulfonyl]-8,9,14,15,24,25,26,26a- octahydro-14-hydroxy-3-isopropyl-4,12-dimethyl-3
1092:
1018:
1114:
900:
765:
753:
569:
565:
558:
65:
251:
924:
883:
861:
Both dalfopristin and quinupristin bind to sites located on the 50S subunit of the
830:
819:
610:
593:
894:
While resistance to dalfopristin may be conferred via a single point of mutation,
934:
and no recommendations by the manufacturer have been made for dose reduction of
927:
for 2–5 days has shown to result in a two-fold increase in cyclosporine levels.
643:
639:
59:
731:
605:
561:
455:
282:
20:
971:
647:
631:
627:
597:
45:
1100:
1056:
1026:
948:
862:
823:
623:
589:
262:
271:
777:
694:
675:
635:
237:
737:
Soluble in ethanol, methanol, DMSO, DMF, and water (0.072 mg/ml)
916:
362:
331:
478:
469:
342:
322:
103:
801:
387:
544:
1038:
1036:
1074:
1072:
1070:
1068:
1066:
930:No adverse effects have been seen in patients with
467:
454:
418:
413:
381:
361:
341:
321:
301:
281:
261:
236:
216:
139:
126:
118:
93:
88:
72:
58:
40:
35:
674:to directly oxidize the sulfur derivative into a
250:
200:-pyrrolo -dioxadiazacyclotetracosine-1,7,16,22(4
225:
972:"Dalfopristin (as mesylate) (CAS 112362-50-2)"
829:activity. However, 8-16 times higher in vitro
807:pKa: 13.18 (Predicted), pKb: 8.97 (Predicted)
689:The production of the dalfopristin portion of
8:
650:group that is available for salt formation.
19:
989:"Synercid (Quinupristin/Dalfopristin) I.V."
701:Physical Characteristics (as mesylate salt)
401:
290:
27:
851:vancomycin-resistant Enterococcus faecium
310:
704:
960:
638:of ostreogrycin A, a structurally more
518:
498:
397:
270:
153:
64:
966:
964:
596:to 70% dalfopristin) is used to treat
18:
983:
981:
370:
350:
50:
7:
994:. U.S. Food and Drug Administration.
662:through achieving a stereoselective
626:of diethylaminoethylthiol to the 2-
586:Rhone-Poulenc Rorer Pharmaceuticals
330:
241:
14:
658:Dalfopristin is synthesized from
974:. Santa Cruz Biotechnology, Inc.
436:
430:
592:(weight-to-weight ratio of 30%
584:) was brought to the market by
580:(marketed under the trade name
526:Key:SUYRLXYYZQTJHF-VMBLUXKRSA-N
1121:Drugs not assigned an ATC code
833:activity is seen against many
448:
442:
424:
1:
1093:10.1016/S0149-2918(01)80028-X
1045:Current Pharmaceutical Design
1019:10.1016/S0149-2918(01)80028-X
818:Alone, both dalfopristin and
938:in this patient population.
919:pathway. Concomitant use of
646:compound contains a readily
564:analogue of ostreogyrcin A (
903:, in over 35 years of use.
1152:
759:940.5 °C at 760 mmHg
414:Chemical and physical data
936:quinupristin/dalfopristin
921:quinupristin/dalfopristin
896:quinupristin/dalfopristin
843:quinupristin/dalfopristin
691:quinupristin/dalfopristin
642:compound is formed. This
578:quinupristin/dalfopristin
534:
509:
489:
144:
26:
52:International Drug Names
873:Mechanism of resistance
654:Large Scale Preparation
1136:Diethylamino compounds
841:are combined . While
835:gram-positive bacteria
814:Antimicrobial activity
713:White to yellow solid
1081:Clinical Therapeutics
1007:Clinical Therapeutics
992:Drug Approval Package
845:is effective against
664:Michael-type addition
889:Enterococcus faecium
611:Enterococcus faecium
576:). The combination
557:is a semi-synthetic
857:Mechanism of action
23:
932:hepatic impairment
660:pristinamycine IIa
942:Commercialization
907:Drug interactions
867:protein synthesis
811:
810:
680:hydrogen peroxide
678:. However, using
672:ruthenium dioxide
570:pristinamycin IIA
552:
551:
480:Interactive image
383:CompTox Dashboard
107:
16:Chemical compound
1143:
1105:
1104:
1076:
1061:
1060:
1040:
1031:
1030:
1002:
996:
995:
985:
976:
975:
968:
790:Refractive index
705:
684:sodium tungstate
670:associated with
668:sodium periodate
548:
547:
540:
482:
462:
450:
444:
438:
432:
426:
406:
405:
391:
389:
374:
354:
334:
314:
294:
274:
254:
244:
243:
229:
192:-21,18-nitrilo-1
131:
105:
102:
68:
54:
31:
24:
22:
1151:
1150:
1146:
1145:
1144:
1142:
1141:
1140:
1111:
1110:
1109:
1108:
1078:
1077:
1064:
1042:
1041:
1034:
1004:
1003:
999:
987:
986:
979:
970:
969:
962:
957:
944:
913:cytochrome P450
909:
875:
859:
816:
703:
656:
620:
574:streptogramin A
566:virginiamycin M
543:
541:
538:(what is this?)
535:
530:
527:
522:
517:
516:
505:
502:
497:
496:
485:
460:
447:
441:
435:
429:
409:
385:
377:
357:
337:
317:
297:
277:
257:
240:
232:
212:
209:
152:
151:
129:
120:Pharmacokinetic
114:
84:
17:
12:
11:
5:
1149:
1147:
1139:
1138:
1133:
1128:
1123:
1113:
1112:
1107:
1106:
1062:
1032:
997:
977:
959:
958:
956:
953:
943:
940:
908:
905:
880:staphylococcal
874:
871:
858:
855:
839:streptogramins
827:bacteriostatic
815:
812:
809:
808:
805:
797:
796:
793:
785:
784:
781:
773:
772:
769:
761:
760:
757:
749:
748:
745:
739:
738:
735:
727:
726:
723:
720:Physical state
715:
714:
711:
702:
699:
655:
652:
619:
616:
550:
549:
532:
531:
529:
528:
525:
523:
520:
512:
511:
510:
507:
506:
504:
503:
500:
492:
491:
490:
487:
486:
484:
483:
475:
473:
465:
464:
458:
452:
451:
445:
439:
433:
427:
422:
416:
415:
411:
410:
408:
407:
399:DTXSID10869549
394:
392:
379:
378:
376:
375:
367:
365:
359:
358:
356:
355:
347:
345:
339:
338:
336:
335:
327:
325:
319:
318:
316:
315:
307:
305:
299:
298:
296:
295:
287:
285:
279:
278:
276:
275:
267:
265:
259:
258:
256:
255:
247:
245:
234:
233:
231:
230:
222:
220:
214:
213:
211:
210:
155:
147:
146:
145:
142:
141:
137:
136:
133:
124:
123:
116:
115:
113:
112:
99:
97:
91:
90:
86:
85:
83:
82:
78:
76:
70:
69:
62:
56:
55:
48:
38:
37:
33:
32:
15:
13:
10:
9:
6:
4:
3:
2:
1148:
1137:
1134:
1132:
1129:
1127:
1124:
1122:
1119:
1118:
1116:
1102:
1098:
1094:
1090:
1086:
1082:
1075:
1073:
1071:
1069:
1067:
1063:
1058:
1054:
1051:(2): 155–80.
1050:
1046:
1039:
1037:
1033:
1028:
1024:
1020:
1016:
1012:
1008:
1001:
998:
993:
990:
984:
982:
978:
973:
967:
965:
961:
954:
952:
950:
941:
939:
937:
933:
928:
926:
922:
918:
914:
906:
904:
902:
901:pristinamycin
897:
892:
890:
885:
881:
872:
870:
868:
864:
856:
854:
852:
848:
847:staphylococci
844:
840:
837:when the two
836:
832:
828:
825:
821:
813:
806:
804:
803:
799:
798:
794:
792:
791:
787:
786:
782:
780:
779:
775:
774:
770:
768:
767:
766:Melting point
763:
762:
758:
756:
755:
754:Boiling point
751:
750:
746:
744:
741:
740:
736:
734:
733:
729:
728:
724:
722:
721:
717:
716:
712:
710:
707:
706:
700:
698:
696:
692:
687:
685:
681:
677:
673:
669:
665:
661:
653:
651:
649:
645:
641:
637:
633:
629:
625:
617:
615:
613:
612:
607:
603:
602:staphylococci
599:
595:
591:
587:
583:
579:
575:
571:
567:
563:
560:
559:streptogramin
556:
546:
539:
533:
524:
519:
515:
508:
499:
495:
488:
481:
477:
476:
474:
471:
466:
459:
457:
453:
423:
421:
417:
412:
404:
400:
396:
395:
393:
384:
380:
373:
372:ChEMBL1200937
369:
368:
366:
364:
360:
353:
349:
348:
346:
344:
340:
333:
329:
328:
326:
324:
320:
313:
309:
308:
306:
304:
300:
293:
289:
288:
286:
284:
280:
273:
269:
268:
266:
264:
260:
253:
249:
248:
246:
239:
235:
228:
224:
223:
221:
219:
215:
207:
203:
199:
195:
191:
187:
183:
179:
175:
171:
167:
163:
159:
154:
150:
143:
138:
134:
132:
125:
121:
117:
111:
101:
100:
98:
96:
92:
87:
80:
79:
77:
75:
71:
67:
63:
61:
57:
53:
49:
47:
43:
39:
36:Clinical data
34:
30:
25:
1087:(1): 24–44.
1084:
1080:
1048:
1044:
1013:(1): 24–44.
1010:
1006:
1000:
991:
945:
929:
925:cyclosporine
910:
893:
884:enterococcal
876:
860:
831:bactericidal
822:have modest
820:quinupristin
817:
800:
788:
776:
771:150 °C
764:
752:
747:-20 °C
742:
730:
718:
708:
688:
657:
622:Through the
621:
609:
594:quinupristin
555:Dalfopristin
554:
553:
542:
536:
205:
201:
197:
193:
189:
185:
181:
177:
173:
169:
165:
161:
157:
128:Elimination
95:Legal status
89:Legal status
21:Dalfopristin
1126:Antibiotics
697:solutions.
644:hydrophobic
640:hydrophobic
608:-resistant
463: g·mol
227:112362-50-2
140:Identifiers
60:MedlinePlus
1115:Categories
955:References
795:n20D 1.58
783:1.27 g/cm
732:Solubility
709:Appearance
630:group and
606:vancomycin
598:infections
562:antibiotic
468:3D model (
456:Molar mass
352:CHEBI:4309
312:R9M4FJE48E
283:ChemSpider
218:CAS Number
149:IUPAC name
802:pK values
648:ionizable
632:oxidation
628:pyrroline
618:Synthesis
588:in 1999.
208:)-tetrone
130:half-life
46:Drugs.com
1131:Oxazoles
1101:11219478
1057:10197038
1027:11219478
949:mesylate
863:ribosome
824:in vitro
624:addition
590:Synercid
582:Synercid
545:(verify)
292:16736919
263:DrugBank
74:ATC code
778:Density
743:Storage
695:acetone
676:sulfone
636:sulfate
634:of the
604:and by
420:Formula
272:DB01764
252:6435782
238:PubChem
66:a603007
1099:
1055:
1025:
951:salt.
917:CYP3A4
725:Solid
494:SMILES
461:690.85
363:ChEMBL
332:D00853
135:1 hour
110:℞-only
108:
923:with
682:with
514:InChI
470:JSmol
343:ChEBI
1097:PMID
1053:PMID
1023:PMID
882:and
849:and
323:KEGG
303:UNII
184:,26a
122:data
81:none
42:AHFS
1089:doi
1015:doi
600:by
388:EPA
242:CID
204:,17
196:,22
180:,26
176:,14
172:,12
168:,10
1117::
1095:.
1085:23
1083:.
1065:^
1047:.
1035:^
1021:.
1011:23
1009:.
980:^
963:^
614:.
572:,
568:,
434:50
428:34
164:,5
160:,4
156:(3
104:US
1103:.
1091::
1059:.
1049:4
1029:.
1017::
472:)
449:S
446:9
443:O
440:4
437:N
431:H
425:C
390:)
386:(
206:H
202:H
198:H
194:H
190:H
186:S
182:R
178:S
174:E
170:E
166:E
162:R
158:R
106::
44:/
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
