Synthesis and biological activity of 6-substituted pyrrolo[2,3-d ]pyrimidine thienoyl regioisomers as inhibitors of de novo purine biosynthesis with selectivity for cellular uptake by high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier

Journal of Medicinal Chemistry

Volumn 55, Issue 4, 2012, Pages 1758-1770

  Wang, Lei ^a   Cherian, Christina ^b,c   Kugel Desmoulin, Sita ^c   Mitchell Ryan, Shermaine ^c   Hou, Zhanjun ^b,c   Matherly, Larry H ^b,c   Gangjee, Aleem ^a  

^a DUQUESNE UNIVERSITY   (United States)

^b KARMANOS CANCER INSTITUTE   (United States)

^c WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [[2 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUT 1 YNYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[2 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUTYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[3 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUT 1 YNYL]THIOPHENE 2 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[3 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUT 1 YNYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[3 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUTYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[4 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUT 1 YNYL]THIOPHENE 2 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[4 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUT 1 YNYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[4 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUTYL]THIOPHENE 2 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[4 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUTYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[5 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUT 1 YNYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; 2 [[5 [4 (2 AMINO 4 OXO 4,7 DIHYDRO 3H PYRROLO[2,3 D] PYRIMIDIN 6 YL)BUTYL]THIOPHENE 3 CARBONYL]AMINO]PENTANEDIOIC ACID; ANTINEOPLASTIC AGENT; CARBON; FOLATE RECEPTOR; FOLINIC ACID; GLUTAMIC ACID; MOLECULAR SCAFFOLD; NUCLEOSIDE; PYRIMIDINE DERIVATIVE; REDUCED FOLATE CARRIER; THIOPHENE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CONCENTRATION (PARAMETERS); CYTOTOXICITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; ISOMER; MEMBRANE TRANSPORT; MOLECULAR DYNAMICS; SUBSTITUTION REACTION;

ALKYNES; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CHO CELLS; CRICETINAE; CRICETULUS; DRUG SCREENING ASSAYS, ANTITUMOR; FOLATE RECEPTOR 1; HUMANS; PROTON-COUPLED FOLATE TRANSPORTER; PURINES; PYRIMIDINES; PYRROLES; REDUCED FOLATE CARRIER PROTEIN; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 84863143908     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201688n     Document Type: Article

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