512:
525:
366:
540:
19:
357:
drugs there has been great interest in developing new drugs in this category. A large number of heterocyclic compounds have been synthesized during related research. These compounds constitute a second generation of PDE inhibitors. Although they have been directed mostly at PDE3, they present
443:: Various substituents have been placed at the para-position of the central phenyl ring. They are electron rich moieties and apparently a positively charged moiety cannot be tolerated in this region of the PDE receptor. There is general agreement about this inhibitor potency:
853:
Boswell-Smith, Victoria; Spina, Domenico; Oxford, Alec W.; Comer, Mike B.; Seeds, Esther A.; Page, Clive P. (August 2006). "The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 isoquinolin-4-one] and RPL565 isoquinolin-4-one]".
554:
Also, meribendan has a higher level of selectivity in comparison with the parent compound CI-930 because, beside the basic nitrogen adjacent to the lactam moiety it possesses another basic nitrogen (benzimidazole ring), opposite to the primary binding site.
273:
Recognition that the knowledge about PDE could be used to develop drugs that were PDE inhibitors led to extensive research. Most studies used analogues of the nucleotide substrates or derivatives of natural product inhibitors such as
1811:
693:
Mizuno, Masashi; Yamano, Shigeki; Chimura, Shuichi; Hirakawa, Atsushi; Takusagawa, Yoshimi; Sawada, Tamotsu; Maetani, Shigeki; Takahashi, Arane; Mizuno, Takeshi; Harada, Kayoko; Shinoda, Asako (20 January 2017).
251:
leads to a positive inotropic effect of PDE3 inhibitors: they increase the force of cardiac contraction. Increased reflux of calcium into the SR following the plateau phase is responsible for their positive
1804:
898:
1797:
945:
437:
and there is general agreement that high affinity PDE3 inhibitors should adopt an energetically favoured planar conformation that mimics the anti conformation of cAMP.
107:. This drug has a much weaker positive inotropic effect than those drugs used for the therapy of acute heart failure, and lacks significant adverse cardiac effects.
638:
970:
938:
1018:
906:
802:
Fossa, Paola; Boggia, Raffaella; Mosti, Luisa (1998). "Toward the identification of the cardiac cGMP inhibited-phosphodiesterase catalytic site".
433:
groups on the heterocycle could be to twist the central ring away from exact coplanarity with the heterocyclic ring. There is a similar twist in
293:
of PDE3 can be considered as a summary of ideas about receptor topography resulting from the first generation inhibitors. The model of the Wells
2143:
931:
1628:
652:
359:
434:
228:
756:
Erhardt, Paul W.; Chou, Yuo-Ling (January 1991). "A topographical model for the c-AMP phosphodiesterase III active site".
399:
there is the presence of a dipole and an adjacent acid proton (an amide function). These atoms are believed to mimic the
1779:
2160:
2060:
1956:
1709:
1605:
954:
217:
404:
104:
2187:
248:
403:
center in the phosphate group in cAMP and are confirmed as the primary site of binding. The heterocycle is a
2148:
696:"Efficacy of pimobendan on survival and reoccurrence of pulmonary edema in canine congestive heart failure"
1935:
1623:
244:
1789:
478:
Identification of features common to the most selective inhibitors has led to a "five-point model" with:
92:, when used for the therapy of acute heart failure, so they have to be applied under close observation.
1462:
811:
136:
1759:
1324:
1224:
1214:
1184:
1121:
1051:
385:
A "heterocycle-phenyl-imidazole" (H-P-I) pattern has been considered to be necessary for positive
2119:
1848:
1538:
1432:
1189:
879:
835:
632:
1734:
1724:
1561:
1422:
1369:
1364:
1349:
1334:
1329:
1314:
1289:
1284:
1279:
1269:
1229:
1111:
1096:
1061:
1003:
548:
528:
1576:
1412:
448:
1820:
1754:
1457:
1359:
1309:
1204:
1086:
871:
827:
773:
725:
671:
571:
46:
34:
1597:
1199:
2109:
1970:
863:
819:
765:
715:
707:
511:
225:
165:
161:
120:
1668:
1477:
240:
232:
157:
74:
815:
656:
88:
are ineffective. Well controlled studies have shown that these drugs generally increase
2154:
1663:
1437:
1417:
1389:
1161:
720:
695:
236:
140:
124:
89:
2181:
2046:
2041:
1888:
1744:
1704:
1613:
1397:
769:
607:(in German). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 454β455, 496.
400:
85:
42:
883:
839:
498:
An electron rich centre and/or a hydrogen bond acceptor site opposite to the dipole.
2114:
1914:
1878:
1838:
1824:
1739:
1678:
1643:
1633:
1543:
1299:
1239:
1081:
672:"Regulation of Phosphodiesterase 3 and Inducible cAMP Early Repressor in the Heart"
524:
515:
389:
activity in cardiac muscle and many second generation inhibitors fit this pattern.
279:
169:
365:
2093:
2078:
2031:
1945:
1919:
1868:
1863:
1833:
1719:
1714:
1673:
1638:
1566:
1533:
1447:
1379:
1339:
1319:
1274:
1234:
1219:
1151:
1146:
1066:
1056:
998:
980:
472:
419:, on the heterocyclic ring usually enhance potency, with occasional exceptions.
416:
396:
370:
354:
290:
257:
132:
128:
923:
2124:
2010:
2000:
1978:
1951:
1909:
1904:
1883:
1729:
1571:
1497:
1472:
1402:
1304:
1249:
1209:
1174:
1169:
1141:
1136:
1116:
1071:
1046:
823:
567:
539:
335:
324:
309:
283:
253:
204:
189:
100:
574:
enzymes PDE-3 and PDE-4. As of
October 2015, inhaled RPL-554 delivered via a
256:
effect: they increase relaxation speed. Additionally, PDE3 inhibitors act as
2129:
2088:
2083:
2036:
2026:
2005:
1940:
1873:
1749:
1683:
1648:
1581:
1515:
1487:
1467:
1442:
1264:
1244:
1126:
1106:
1101:
1076:
1036:
975:
867:
575:
386:
378:
331:
313:
302:
221:
199:
194:
81:
70:
66:
22:
875:
729:
831:
777:
2073:
1994:
1764:
1699:
1658:
1618:
1492:
1407:
1344:
1294:
1254:
1179:
1041:
1013:
711:
483:
456:
452:
275:
184:
62:
1452:
1427:
1354:
1259:
1194:
1131:
899:"Verona sets sights on PhIIb after COPD drug comes through early trial"
563:
18:
1482:
1374:
1091:
464:
444:
426:
412:
374:
317:
297:
version as cited in
Erhardt and Chou (1991) includes the following:
1591:
1553:
538:
523:
510:
468:
460:
430:
408:
364:
17:
1653:
1525:
1507:
1008:
990:
962:
38:
1793:
927:
224:
3 leads to an increase of intracellular concentrations of the
207:(approved for human use in Japan, approved for dogs elsewhere)
578:
was in development for COPD and had been studied in asthma.
856:
The
Journal of Pharmacology and Experimental Therapeutics
492:
A small sized alkyl substituent on the heterocyclic ring.
429:, needs to be present. The beneficial effects of small
625:
353:
Since selective PDE3 inhibitors were recognised to be
160:
when used for the therapy of acute heart failure are
547:
Theophylline is a non-selective agent. In contrast,
2102:
2059:
2019:
1987:
1969:
1928:
1897:
1856:
1847:
1832:
1692:
1604:
1590:
1552:
1524:
1506:
1388:
1160:
1027:
989:
961:
459:in the analogous 4 position β₯ alkyl-S- > simple
603:Mutschler, Ernst; SchΓ€fer-Korting, Monika (1997).
570:, and like trequinsin, is a dual inhibitor of the
25:, one of the first PDE3 inhibitors used clinically
425:: It seems that an electron rich centre, such as
180:Approved PDE3 inhibitors include the following:
73:are used clinically for short-term treatment of
247:(SR) during phase 2 (the plateau phase) of the
1805:
939:
8:
598:
596:
594:
592:
590:
33:is a drug which inhibits the action of the
1853:
1844:
1812:
1798:
1790:
946:
932:
924:
804:Journal of Computer-Aided Molecular Design
637:: CS1 maint: location missing publisher (
84:for the therapy of acute heart failure if
751:
749:
747:
745:
743:
741:
739:
719:
700:The Journal of Veterinary Medical Science
543:CI-930, the parent compound of meribendan
41:. They are used for the therapy of acute
655:. FDA. 25 September 2006. Archived from
455:in place of the central phenyl with its
797:
795:
793:
791:
789:
787:
618:
616:
614:
586:
243:. An increased calcium influx from the
630:
77:in the presence of cardiogenic shock.
503:Examples of selective PDE3 inhibitors
495:A relatively flat overall topography.
7:
897:Taylor, Nick Paul (1 October 2015).
486:moiety) at one end of the molecule.
239:, which in turn activates cardiac
14:
627:(in German). Munich. p. 457.
623:Forth; Henschler; Rummel (2002).
551:is a highly selective inhibitor.
349:Second generation PDE3 inhibitors
80:PDE3 inhibitors are indicated as
269:First generation PDE3 inhibitors
143:is prohibited during treatment.
360:structure-activity relationship
1823:excluding cardiac glycosides (
531:, a highly selective inhibitor
506:
229:cyclic adenosine monophosphate
216:PDE3 inhibitors are a type of
1:
1780:Receptor/signaling modulators
482:Presence of a strong dipole (
475:(which is totally inactive).
103:is used for the treatment of
2061:Phosphodiesterase inhibitors
955:Phosphodiesterase inhibitors
770:10.1016/0024-3205(91)90254-9
334:binding site portion of the
218:phosphodiesterase inhibitors
518:, a non-selective inhibitor
344:An area with bulk tolerance
312:area that accommodates the
2204:
411:groups, limited to either
341:A sterically hindered site
231:(cAMP). cAMP mediates the
2138:
1773:
405:transition state analogue
362:for the PDEs in general.
105:intermittent claudication
96:Peripheral artery disease
2103:Other cardiac stimulants
653:"Approval of Cilostazol"
489:An adjacent acid proton.
249:cardiac action potential
220:. Inhibition of the PDE
868:10.1124/jpet.105.099192
824:10.1023/a:1007928412086
123:are severe obstructive
1936:Amezinium metilsulfate
1624:Choline theophyllinate
674:. Circulation Research
544:
532:
519:
393:The heterocycle region
382:
245:sarcoplasmic reticulum
26:
1042:Amrinone (inamrinone)
605:Arzneimittelwirkungen
542:
527:
514:
368:
21:
712:10.1292/jvms.16-0069
441:The imidazole region
137:ventricular aneurysm
1849:Adrenergic agonists
816:1998JCAMD..12..361F
381:) pattern of CI-930
264:Chemical properties
212:Mechanism of action
156:The most important
2165:Never to phase III
2120:Omecamtiv mecarbil
1821:Cardiac stimulants
545:
533:
520:
407:inhibitor of PDE.
383:
27:
2175:
2174:
2055:
2054:
2020:Unknown/ungrouped
1971:Dopamine agonists
1965:
1964:
1787:
1786:
1458:Nitrosoprodenafil
659:on 27 April 2007.
572:phosphodiesterase
537:
536:
423:The phenyl region
121:Contraindications
111:Contraindications
47:cardiogenic shock
35:phosphodiesterase
2195:
2110:Angiotensinamide
1854:
1845:
1814:
1807:
1800:
1791:
948:
941:
934:
925:
919:
918:
916:
914:
905:. Archived from
894:
888:
887:
850:
844:
843:
799:
782:
781:
753:
734:
733:
723:
690:
684:
683:
681:
679:
667:
661:
660:
649:
643:
642:
636:
628:
620:
609:
608:
600:
566:is an analog of
507:
447:β₯ alkyl-CONH- β₯
241:calcium channels
226:second messenger
166:thrombocytopenia
2203:
2202:
2198:
2197:
2196:
2194:
2193:
2192:
2188:PDE3 inhibitors
2178:
2177:
2176:
2171:
2170:
2155:Clinical trials
2134:
2098:
2051:
2015:
1983:
1961:
1924:
1893:
1837:
1828:
1818:
1788:
1783:
1769:
1688:
1669:Propentofylline
1600:
1586:
1548:
1520:
1502:
1478:Sulfoaildenafil
1463:Norcarbodenafil
1384:
1156:
1023:
985:
957:
952:
922:
912:
910:
909:on 7 March 2016
896:
895:
891:
852:
851:
847:
801:
800:
785:
755:
754:
737:
692:
691:
687:
677:
675:
669:
668:
664:
651:
650:
646:
629:
622:
621:
612:
602:
601:
588:
584:
561:
505:
351:
271:
266:
237:protein kinases
233:phosphorylation
214:
178:
158:adverse effects
154:
149:
147:Adverse effects
118:
113:
98:
75:cardiac failure
60:
55:
12:
11:
5:
2201:
2199:
2191:
2190:
2180:
2179:
2173:
2172:
2169:
2168:
2167:
2166:
2163:
2152:
2146:
2140:
2139:
2136:
2135:
2133:
2132:
2127:
2122:
2117:
2112:
2106:
2104:
2100:
2099:
2097:
2096:
2091:
2086:
2081:
2076:
2070:
2068:
2057:
2056:
2053:
2052:
2050:
2049:
2044:
2039:
2034:
2029:
2023:
2021:
2017:
2016:
2014:
2013:
2008:
2003:
1998:
1991:
1989:
1985:
1984:
1982:
1981:
1975:
1973:
1967:
1966:
1963:
1962:
1960:
1959:
1957:Norepinephrine
1954:
1949:
1943:
1938:
1932:
1930:
1926:
1925:
1923:
1922:
1917:
1912:
1907:
1901:
1899:
1895:
1894:
1892:
1891:
1886:
1881:
1876:
1871:
1866:
1860:
1858:
1851:
1842:
1830:
1829:
1819:
1817:
1816:
1809:
1802:
1794:
1785:
1784:
1774:
1771:
1770:
1768:
1767:
1762:
1757:
1752:
1747:
1742:
1737:
1732:
1727:
1722:
1717:
1712:
1707:
1702:
1696:
1694:
1690:
1689:
1687:
1686:
1681:
1676:
1671:
1666:
1664:Pentoxifylline
1661:
1656:
1651:
1646:
1641:
1636:
1631:
1626:
1621:
1616:
1610:
1608:
1602:
1601:
1596:
1594:
1588:
1587:
1585:
1584:
1579:
1574:
1569:
1564:
1558:
1556:
1550:
1549:
1547:
1546:
1541:
1536:
1530:
1528:
1522:
1521:
1519:
1518:
1512:
1510:
1504:
1503:
1501:
1500:
1495:
1490:
1485:
1480:
1475:
1470:
1465:
1460:
1455:
1450:
1445:
1440:
1438:Homosildenafil
1435:
1430:
1425:
1420:
1418:Benzamidenafil
1415:
1410:
1405:
1400:
1394:
1392:
1386:
1385:
1383:
1382:
1377:
1372:
1367:
1362:
1357:
1352:
1347:
1342:
1337:
1332:
1327:
1322:
1317:
1312:
1307:
1302:
1297:
1292:
1287:
1282:
1277:
1272:
1267:
1262:
1257:
1252:
1247:
1242:
1237:
1232:
1227:
1222:
1217:
1212:
1207:
1202:
1197:
1192:
1187:
1182:
1177:
1172:
1166:
1164:
1158:
1157:
1155:
1154:
1149:
1144:
1139:
1134:
1129:
1124:
1119:
1114:
1109:
1104:
1099:
1094:
1089:
1084:
1079:
1074:
1069:
1064:
1059:
1054:
1049:
1044:
1039:
1033:
1031:
1025:
1024:
1022:
1021:
1016:
1011:
1006:
1001:
995:
993:
987:
986:
984:
983:
978:
973:
967:
965:
959:
958:
953:
951:
950:
943:
936:
928:
921:
920:
889:
862:(2): 840β848.
845:
810:(4): 361β372.
783:
764:(8): 553β568.
735:
685:
662:
644:
610:
585:
583:
580:
560:
557:
535:
534:
521:
504:
501:
500:
499:
496:
493:
490:
487:
395:: Within each
350:
347:
346:
345:
342:
339:
328:
321:
306:
270:
267:
265:
262:
213:
210:
209:
208:
202:
197:
192:
187:
177:
174:
168:and increased
153:
150:
148:
145:
141:Breast feeding
125:cardiomyopathy
117:
114:
112:
109:
97:
94:
86:catecholamines
59:
56:
54:
51:
31:PDE3 inhibitor
13:
10:
9:
6:
4:
3:
2:
2200:
2189:
2186:
2185:
2183:
2164:
2162:
2159:
2158:
2156:
2153:
2150:
2147:
2145:
2142:
2141:
2137:
2131:
2128:
2126:
2123:
2121:
2118:
2116:
2113:
2111:
2108:
2107:
2105:
2101:
2095:
2092:
2090:
2087:
2085:
2082:
2080:
2077:
2075:
2072:
2071:
2069:
2066:
2062:
2058:
2048:
2047:Theodrenaline
2045:
2043:
2042:Mephentermine
2040:
2038:
2035:
2033:
2030:
2028:
2025:
2024:
2022:
2018:
2012:
2009:
2007:
2004:
2002:
1999:
1996:
1993:
1992:
1990:
1986:
1980:
1977:
1976:
1974:
1972:
1968:
1958:
1955:
1953:
1950:
1947:
1944:
1942:
1939:
1937:
1934:
1933:
1931:
1927:
1921:
1918:
1916:
1913:
1911:
1908:
1906:
1903:
1902:
1900:
1896:
1890:
1889:Phenylephrine
1887:
1885:
1882:
1880:
1877:
1875:
1872:
1870:
1867:
1865:
1862:
1861:
1859:
1855:
1852:
1850:
1846:
1843:
1840:
1835:
1831:
1826:
1822:
1815:
1810:
1808:
1803:
1801:
1796:
1795:
1792:
1782:
1781:
1778:
1772:
1766:
1763:
1761:
1758:
1756:
1753:
1751:
1748:
1746:
1745:Proxyphylline
1743:
1741:
1738:
1736:
1733:
1731:
1728:
1726:
1723:
1721:
1718:
1716:
1713:
1711:
1708:
1706:
1705:Diprophylline
1703:
1701:
1698:
1697:
1695:
1691:
1685:
1682:
1680:
1677:
1675:
1672:
1670:
1667:
1665:
1662:
1660:
1657:
1655:
1652:
1650:
1647:
1645:
1642:
1640:
1637:
1635:
1632:
1630:
1627:
1625:
1622:
1620:
1617:
1615:
1614:Aminophylline
1612:
1611:
1609:
1607:
1606:Non-selective
1603:
1599:
1595:
1593:
1589:
1583:
1580:
1578:
1575:
1573:
1570:
1568:
1565:
1563:
1560:
1559:
1557:
1555:
1551:
1545:
1542:
1540:
1537:
1535:
1532:
1531:
1529:
1527:
1523:
1517:
1514:
1513:
1511:
1509:
1505:
1499:
1496:
1494:
1491:
1489:
1486:
1484:
1481:
1479:
1476:
1474:
1471:
1469:
1466:
1464:
1461:
1459:
1456:
1454:
1451:
1449:
1446:
1444:
1441:
1439:
1436:
1434:
1431:
1429:
1426:
1424:
1421:
1419:
1416:
1414:
1411:
1409:
1406:
1404:
1401:
1399:
1398:Acetildenafil
1396:
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1381:
1378:
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929:
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904:
903:FierceBiotech
900:
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758:Life Sciences
752:
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736:
731:
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709:
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619:
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454:
450:
446:
442:
438:
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432:
428:
424:
420:
418:
414:
410:
406:
402:
401:electrophilic
398:
394:
390:
388:
380:
376:
372:
367:
363:
361:
356:
348:
343:
340:
337:
333:
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134:
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126:
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115:
110:
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95:
93:
91:
87:
83:
78:
76:
72:
68:
64:
57:
52:
50:
48:
44:
43:heart failure
40:
36:
32:
24:
20:
16:
2115:Levosimendan
2064:
1915:Isoprenaline
1879:Norfenefrine
1839:dopaminergic
1776:
1775:
1760:Tolafentrine
1740:Pentifylline
1679:Theophylline
1644:Enprofylline
1634:Dipyridamole
1544:Paraxanthine
1325:Pumafentrine
1300:Mesembrenone
1240:Ensifentrine
1225:Denbutylline
1215:Cipamfylline
1185:Benafentrine
1122:Pumafentrine
1082:Ensifentrine
1052:Benafentrine
1028:
911:. Retrieved
907:the original
902:
892:
859:
855:
848:
807:
803:
761:
757:
706:(1): 29β34.
703:
699:
688:
676:. Retrieved
665:
657:the original
647:
624:
604:
562:
553:
546:
516:Theophylline
477:
440:
439:
422:
421:
392:
391:
384:
358:significant
352:
338:binding site
327:binding site
316:side of the
305:binding area
294:
288:
280:theophylline
272:
258:vasodilators
215:
179:
170:transaminase
155:
119:
99:
79:
61:
53:Medical uses
30:
28:
15:
2151:from market
2094:Vesnarinone
2079:Bucladesine
2032:Dimetofrine
1946:Epinephrine
1920:Prenalterol
1869:Methoxamine
1864:Metaraminol
1720:Lisofylline
1715:Furafylline
1674:Theobromine
1639:Doxofylline
1567:Mardepodect
1539:PF-04447943
1534:BAY 73-6691
1448:Mirodenafil
1433:Gisadenafil
1380:Zardaverine
1340:Roflumilast
1320:Piclamilast
1275:Irsogladine
1235:Drotaverine
1220:Crisaborole
1190:Catramilast
1152:Zardaverine
1147:Vesnarinone
1067:Cilostamide
1057:Bucladesine
999:BAY 60-7550
981:Vinpocetine
670:Yan, Chen.
473:imidazolium
397:heterocycle
371:heterocycle
355:cardiotonic
291:active site
133:tachycardia
129:hypovolemia
2125:Pimobendan
2011:Octopamine
2001:Dopexamine
1979:Fenoldopam
1952:Etilefrine
1910:Dobutamine
1905:Arbutamine
1834:Adrenergic
1735:Oxagrelate
1730:Moxaverine
1725:MDL-12330A
1572:Papaverine
1562:Balipodect
1498:Vardenafil
1473:Sildenafil
1423:Dasantafil
1403:Aildenafil
1370:Tofimilast
1365:Tetomilast
1350:Ronomilast
1335:Ro 20-1724
1330:Revamilast
1315:Oglemilast
1305:Mesembrine
1290:Lotamilast
1285:Lirimilast
1280:Lavamilast
1270:Indimilast
1250:Filaminast
1230:Difamilast
1210:Cilomilast
1175:Arofylline
1170:Apremilast
1142:Trequinsin
1137:Siguazodan
1117:Pimobendan
1112:Parogrelil
1097:Meribendan
1072:Cilostazol
1062:Carbazeran
1047:Anagrelide
1004:Carbazeran
678:23 January
582:References
568:trequinsin
549:meribendan
529:Meribendan
336:pyrimidine
325:pyrimidine
310:lipophilic
284:papaverine
254:lusitropic
205:pimobendan
190:cilostazol
162:arrhythmia
101:Cilostazol
82:inotropics
2161:Phase III
2149:Withdrawn
2130:Xamoterol
2089:Milrinone
2084:Enoximone
2037:Gepefrine
2027:Cafedrine
2006:Ibopamine
1941:Droxidopa
1874:Midodrine
1777:See also:
1750:Quercetin
1684:Zaprinast
1649:Ibudilast
1582:Tofisopam
1577:TC-E 5005
1516:BRL-50481
1488:Tadalafil
1468:SCH-51866
1443:Lodenafil
1413:Beminafil
1265:ICI-63197
1245:Etazolate
1127:Quazinone
1107:Olprinone
1102:Milrinone
1077:Enoximone
1037:Adibendan
976:SCH-51866
633:cite book
576:nebulizer
449:imidazoyl
387:inotropic
379:imidazole
332:imidazole
314:non-polar
303:phosphate
222:isoenzyme
200:enoximone
195:milrinone
90:mortality
71:enoximone
67:milrinone
23:Milrinone
2182:Category
2074:Amrinone
1995:Dopamine
1884:Oxedrine
1765:Trapidil
1755:Satigrel
1700:Diazepam
1693:Unsorted
1659:Luteolin
1619:Caffeine
1493:Udenafil
1408:Avanafil
1360:RS-25344
1345:Rolipram
1310:Mesopram
1295:Luteolin
1255:Glaucine
1205:CGH-2466
1180:Atizoram
1087:Imazodan
1014:Oxindole
884:15490792
876:16682455
840:34807211
730:27644192
559:Research
484:carbonyl
457:nitrogen
453:pyridine
276:xanthine
185:amrinone
172:levels.
63:Amrinone
1598:BC11-38
1453:MY-5445
1428:Icariin
1355:RPL-554
1260:HT-0712
1200:CDP-840
1195:CC-1088
1132:RPL-554
913:2 March
832:9777494
812:Bibcode
778:1650876
721:5289233
564:RPL-554
377:) β I (
373:) β P (
152:Cardiac
116:Cardiac
58:Cardiac
37:enzyme
2144:WHO-EM
1841:agents
1483:T-0156
1375:YM-976
1092:KMUP-1
882:
874:
838:
830:
776:
728:
718:
465:halide
445:lactam
427:phenyl
413:methyl
375:phenyl
320:moiety
318:ribose
295:et al.
282:) and
278:(e.g.
135:, and
2065:PDE3I
1929:mixed
1710:DPCPX
1592:PDE11
1554:PDE10
880:S2CID
836:S2CID
471:>
469:amine
463:>
461:ether
431:alkyl
417:ethyl
409:Alkyl
176:Types
1988:Both
1825:C01C
1654:IBMX
1526:PDE9
1508:PDE7
1390:PDE5
1162:PDE4
1029:PDE3
1009:EHNA
991:PDE2
971:MMPX
963:PDE1
915:2016
872:PMID
828:PMID
774:PMID
726:PMID
680:2016
639:link
435:cAMP
289:The
69:and
45:and
39:PDE3
1836:and
1629:CPX
1019:PDP
864:doi
860:318
820:doi
766:doi
716:PMC
708:doi
415:or
369:H (
330:An
235:of
2184::
2157::
901:.
878:.
870:.
858:.
834:.
826:.
818:.
808:12
806:.
786:^
772:.
762:49
760:.
738:^
724:.
714:.
704:79
702:.
698:.
635:}}
631:{{
613:^
589:^
467:=
451:=
323:A
308:A
301:A
286:.
260:.
164:,
139:.
131:,
127:,
65:,
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29:A
2067:)
2063:(
1997:#
1948:#
1898:Ξ²
1857:Ξ±
1827:)
1813:e
1806:t
1799:v
947:e
940:t
933:v
917:.
886:.
866::
842:.
822::
814::
780:.
768::
732:.
710::
682:.
641:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
