Novel and potent calcium-sensing receptor antagonists: Discovery of (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6, 7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate (TAK-075) as an orally active bone anabolic agent

Bioorganic and Medicinal Chemistry

Volumn 19, Issue 6, 2011, Pages 1881-1894

  Yoshida, Masato ^a   Mori, Akira ^a   Morimoto, Shinji ^a   Kotani, Etsuo ^a   Oka, Masahiro ^a   Notoya, Kohei ^a   Makino, Haruhiko ^a   Ono, Midori ^a   Shirasaki, Mikio ^a   Tada, Norio ^a   Fujita, Hisashi ^a   Ban, Junko ^a   Ikeda, Yukihiro ^a   Kawamoto, Tomohiro ^a   Goto, Mika ^a   Kimura, Hiroyuki ^a   Baba, Atsuo ^a   Yasuma, Tsuneo ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

Bone anabolic agents; Calcium sensing receptor antagonists; CaSR; Orally active; PTH; TAK 075

Indexed keywords

2 BENZYL 7,7 DIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDRODROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; 2 BENZYL N [1 ETHYL 1 (4 METHYLPHENYL)PROPYL] 7,7 DIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; 2 BUTYL 7,7 DIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; 2 BUTYL N [1 ETHYL 1 (4 METHYLPHENYL)PROPYL] 7,7 DIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; 2 ETHYL 7,7 DIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLO[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; 2,7,7 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE ACID; 2,7,7 TRIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLO[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; 7,7 DIMETHYL 2 (METHYLTHIO) 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; 7,7 DIMETHYL 2,5 DIPHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; 7,7 DIMETHYL 5 PHENYL 2 PROPYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ANABOLIC AGENT; CALCIUM SENSING RECEPTOR; ETHYL 2 BENZYL 7,7 DIMETHYL 5 PHENYL 4,7 DIHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ETHYL 2 BENZYL 7,7 DIMETHYL 5 PHENYL 4,7 TETRAHYDRODROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ETHYL 2 BUTYL 7,7 DIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ETHYL 2 BUTYL 7,7 DIMETHYL 5 PHENYL 4,7 DIHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ETHYL 7,7 DIMETHYL 2,5 DIPHENYL 4,5,6,7 TETRAHYROHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ETHYL 7,7 DIMETHYL 2,5 DIPHENYL 4,7 DIHYROHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ETHYL 7,7 DIMETHYL 5 PHENYL 2 PROPYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; ETHYL 7,7 DIMETHYL 5 PHENYL 2 PROPYL 4,7 DIHYDROPYRAZOLO[1,5 A]PYRIMIDINE 3 CARBOXYCYLIC ACID; N [1 ETHYL 1 (4 ETHYLPHENYL)PROPYL] 2,7,7 TRIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLO[1,5 A]PYRIMIDINE 3 CARBOXAMIDE MONOTOSYLATE; N [1 ETHYL 1 (4 ETHYLPHENYL)PROPYL] 2,7,7 TRIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; N [1 ETHYL 1 (4 METHYPHENYL)PROPYL] 2,7,7 TRIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; N [1 ETHYL 1 (4 METHYPHENYL)PROPYL] 7,7 DIMETHYL (METHYLTHIO) 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; N [1 ETHYL 1 (4 METHYPHENYL)PROPYL] 7,7 DIMETHYL 2,5 DIPHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; N [1 ETHYL 1 (4 METHYPHENYL)PROPYL] 7,7 DIMETHYL 5 PHENYL 2 PROPYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; N [1 ETHYL 1 (4 METHYPHENYL)PROPYL] 7,7 DIMETHYL 5 PHENYL 4,5,6,7 TETRAHYDROPYRAZOLOL[1,5 A]PYRIMIDINE 3 CARBOXAMIDE HYDROCHLORIDE; TAK 075; TETRAHYDROPYRAZOLOPYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SOLUBILITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; HUMAN; IC 50; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; STEREOCHEMISTRY; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ANABOLIC AGENTS; ANIMALS; CRYSTALLOGRAPHY, X-RAY; DRUG EVALUATION, PRECLINICAL; HUMANS; MACACA FASCICULARIS; MOLECULAR CONFORMATION; OSTEOPOROSIS; PARATHYROID HORMONE; PYRAZOLES; PYRIMIDINES; RATS; RECEPTORS, CALCIUM-SENSING;

RATTUS;

EID: 79952453311     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2011.02.001     Document Type: Article

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22. The practical synthesis of TAK-075 will be reported in due course.