CA2458661A1 - Methods of increasing endogenous testosterone levels - Google Patents
Methods of increasing endogenous testosterone levels Download PDFInfo
- Publication number
- CA2458661A1 CA2458661A1 CA002458661A CA2458661A CA2458661A1 CA 2458661 A1 CA2458661 A1 CA 2458661A1 CA 002458661 A CA002458661 A CA 002458661A CA 2458661 A CA2458661 A CA 2458661A CA 2458661 A1 CA2458661 A1 CA 2458661A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- pyrazol
- pyridin
- butylphenyl
- tyrosinamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims description 63
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 title abstract description 89
- 229960003604 testosterone Drugs 0.000 title abstract description 45
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
- 208000035475 disorder Diseases 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 69
- -1 substituted pyrazole compound Chemical class 0.000 claims description 53
- PQFMNVGMJJMLAE-QMMMGPOBSA-N L-tyrosinamide Chemical compound NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PQFMNVGMJJMLAE-QMMMGPOBSA-N 0.000 claims description 51
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 44
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 38
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 35
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 35
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 20
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 20
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 20
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- 150000001413 amino acids Chemical class 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 17
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 16
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 14
- 150000003973 alkyl amines Chemical class 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 13
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 13
- 206010002261 Androgen deficiency Diseases 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 125000002723 alicyclic group Chemical group 0.000 claims description 10
- 125000004450 alkenylene group Chemical group 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004419 alkynylene group Chemical group 0.000 claims description 9
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 8
- JFAZHJWWPOJMOJ-MHZLTWQESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4-(2-butyl-5-isoquinolin-3-ylpyrazol-3-yl)benzamide Chemical compound C([C@H](N)C(=O)NC(=O)C1=CC=C(C=C1)C1=CC(=NN1CCCC)C=1N=CC2=CC=CC=C2C=1)C1=CC=C(O)C=C1 JFAZHJWWPOJMOJ-MHZLTWQESA-N 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 150000003862 amino acid derivatives Chemical class 0.000 claims description 5
- 230000021595 spermatogenesis Effects 0.000 claims description 5
- MGOGKPMIZGEGOZ-REOHCLBHSA-N (2s)-2-amino-3-hydroxypropanamide Chemical compound OC[C@H](N)C(N)=O MGOGKPMIZGEGOZ-REOHCLBHSA-N 0.000 claims description 4
- WVROHOIVYGRGME-LJAQVGFWSA-N (2s)-n-acetyl-2-amino-n-[3-[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]propyl]-3-(4-hydroxyphenyl)propanamide Chemical compound O=C([C@@H](N)CC=1C=CC(O)=CC=1)N(C(=O)C)CCCC1=CC(C=2C=CN=CC=2)=NN1C1=CC=C(C(C)(C)C)C=C1 WVROHOIVYGRGME-LJAQVGFWSA-N 0.000 claims description 4
- TUEXMSFXLWQHFG-UHFFFAOYSA-N 4-[2-[3-[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]propylamino]ethyl]phenol Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCNCCC=2C=CC(O)=CC=2)=CC(C=2C=CN=CC=2)=N1 TUEXMSFXLWQHFG-UHFFFAOYSA-N 0.000 claims description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
- 239000002871 fertility agent Substances 0.000 claims description 3
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 210000003205 muscle Anatomy 0.000 claims description 3
- HKHSNOVJWZUIRS-YTTGMZPUSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-3-[5-isoquinolin-3-yl-2-(4-propylphenyl)pyrazol-3-yl]benzamide Chemical compound C1=CC(CCC)=CC=C1N1C(C=2C=C(C=CC=2)C(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2N=CC3=CC=CC=C3C=2)=N1 HKHSNOVJWZUIRS-YTTGMZPUSA-N 0.000 claims description 3
- MOYZXLIYLRFLEY-MHZLTWQESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-5-[2-(4-tert-butylphenyl)-5-pyridin-2-ylpyrazol-3-yl]pentanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2N=CC=CC=2)=N1 MOYZXLIYLRFLEY-MHZLTWQESA-N 0.000 claims description 3
- ZBVGKFZYFFMQJP-NDEPHWFRSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-5-[2-(4-tert-butylphenyl)-5-pyridin-3-ylpyrazol-3-yl]pentanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=NC=CC=2)=N1 ZBVGKFZYFFMQJP-NDEPHWFRSA-N 0.000 claims description 3
- MUCNBPCTSRYLCB-UHFFFAOYSA-N n-[2-(4-hydroxyphenyl)ethyl]benzamide Chemical compound C1=CC(O)=CC=C1CCNC(=O)C1=CC=CC=C1 MUCNBPCTSRYLCB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
- 125000005556 thienylene group Chemical group 0.000 claims description 3
- APCIEEOJYLJUPD-SANMLTNESA-N (2s)-2-amino-n-[3-[[2-(4-tert-butylphenyl)-5-pyridin-3-ylpyrazol-3-yl]amino]propyl]-3-(4-hydroxyphenyl)propanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(NCCCNC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=NC=CC=2)=N1 APCIEEOJYLJUPD-SANMLTNESA-N 0.000 claims description 2
- WDDUAPAZOKCCTQ-NDEPHWFRSA-N (2s)-n-acetyl-2-amino-n-[3-[[2-(4-tert-butylphenyl)-5-pyridin-3-ylpyrazol-3-yl]amino]propyl]-3-(4-hydroxyphenyl)propanamide Chemical compound O=C([C@@H](N)CC=1C=CC(O)=CC=1)N(C(=O)C)CCCNC1=CC(C=2C=NC=CC=2)=NN1C1=CC=C(C(C)(C)C)C=C1 WDDUAPAZOKCCTQ-NDEPHWFRSA-N 0.000 claims description 2
- MZYKZNKHAVHVKD-UHFFFAOYSA-N 3-[4-[[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]amino]butanoylamino]-4-(4-hydroxyphenyl)butanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(NCCCC(=O)NC(CC(N)=O)CC=2C=CC(O)=CC=2)=CC(C=2C=CN=CC=2)=N1 MZYKZNKHAVHVKD-UHFFFAOYSA-N 0.000 claims description 2
- NXFAJZOAGVIHSJ-RSXGOPAZSA-N 6-[2-(4-propan-2-ylphenyl)-5-pyridin-2-ylpyrazol-3-yl]-n-[(2s,3r)-2,3,4-trihydroxybutanoyl]hexanamide Chemical compound C1=CC(C(C)C)=CC=C1N1C(CCCCCC(=O)NC(=O)[C@@H](O)[C@H](O)CO)=CC(C=2N=CC=CC=2)=N1 NXFAJZOAGVIHSJ-RSXGOPAZSA-N 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- AKGOXGFNEQXHLO-MHZLTWQESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4-[[2-(4-tert-butylphenyl)-5-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrazol-3-yl]amino]butanamide Chemical compound C1N(C)CCC(C2=NN(C(NCCCC(=O)NC(=O)[C@@H](N)CC=3C=CC(O)=CC=3)=C2)C=2C=CC(=CC=2)C(C)(C)C)=C1 AKGOXGFNEQXHLO-MHZLTWQESA-N 0.000 claims description 2
- PYTQWRKGOQPYAC-MHZLTWQESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4-[[2-(4-tert-butylphenyl)-5-(1-methyl-3,6-dihydro-2h-pyridin-5-yl)pyrazol-3-yl]amino]butanamide Chemical compound C1N(C)CCC=C1C1=NN(C=2C=CC(=CC=2)C(C)(C)C)C(NCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=C1 PYTQWRKGOQPYAC-MHZLTWQESA-N 0.000 claims description 2
- MZCIVIOZXSOCRG-SANMLTNESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4-[[2-(4-tert-butylphenyl)-5-(1-oxidopyridin-1-ium-4-yl)pyrazol-3-yl]amino]butanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(NCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=C[N+]([O-])=CC=2)=N1 MZCIVIOZXSOCRG-SANMLTNESA-N 0.000 claims description 2
- HELSTEXWEVIMGG-SANMLTNESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4-[[2-(4-tert-butylphenyl)-5-pyridin-3-ylpyrazol-3-yl]amino]butanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(NCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=NC=CC=2)=N1 HELSTEXWEVIMGG-SANMLTNESA-N 0.000 claims description 2
- AGOGBVNCDFQRKD-NDEPHWFRSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4-[[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]amino]-n-(2-hydroxyethyl)butanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(NCCCC(=O)N(CCO)C(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=CN=CC=2)=N1 AGOGBVNCDFQRKD-NDEPHWFRSA-N 0.000 claims description 2
- ZTVKPKWQZYDCLI-OQGPVULJSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4-[[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]amino]-n-[2-(1-methylpyrrolidin-2-yl)ethyl]butanamide Chemical compound CN1CCCC1CCN(C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C(=O)CCCNC1=CC(C=2C=CN=CC=2)=NN1C1=CC=C(C(C)(C)C)C=C1 ZTVKPKWQZYDCLI-OQGPVULJSA-N 0.000 claims description 2
- CNTOCNZGKGCKCG-MHZLTWQESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-5-[2-(4-propan-2-ylphenyl)-5-pyridin-2-ylpyrazol-3-yl]pentanamide Chemical compound C1=CC(C(C)C)=CC=C1N1C(CCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2N=CC=CC=2)=N1 CNTOCNZGKGCKCG-MHZLTWQESA-N 0.000 claims description 2
- DWWZNYXSTZFKAP-DEOSSOPVSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-5-[2-(4-propan-2-ylphenyl)-5-pyridin-2-ylpyrazol-3-yl]thiophene-2-carboxamide Chemical compound C1=CC(C(C)C)=CC=C1N1C(C=2SC(=CC=2)C(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2N=CC=CC=2)=N1 DWWZNYXSTZFKAP-DEOSSOPVSA-N 0.000 claims description 2
- YWBKOZLVOMXEAJ-NDEPHWFRSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-5-[2-(4-propan-2-ylphenyl)-5-pyridin-3-ylpyrazol-3-yl]pentanamide Chemical compound C1=CC(C(C)C)=CC=C1N1C(CCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=NC=CC=2)=N1 YWBKOZLVOMXEAJ-NDEPHWFRSA-N 0.000 claims description 2
- CCHPYCQKMSYGPQ-HKBQPEDESA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-5-[2-(4-tert-butylphenyl)-5-isoquinolin-3-ylpyrazol-3-yl]pentanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2N=CC3=CC=CC=C3C=2)=N1 CCHPYCQKMSYGPQ-HKBQPEDESA-N 0.000 claims description 2
- LRSWZRMHQCKTGM-NDEPHWFRSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-6-[2-(4-tert-butylphenyl)-5-pyridin-2-ylpyrazol-3-yl]hexanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2N=CC=CC=2)=N1 LRSWZRMHQCKTGM-NDEPHWFRSA-N 0.000 claims description 2
- NSFBBHBQTOEQBG-LJAQVGFWSA-N n-[(2s)-2-amino-3-[4-(hydroxymethyl)phenyl]propanoyl]-6-[2-(4-tert-butylphenyl)-5-pyridin-2-ylpyrazol-3-yl]hexanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(CO)=CC=2)=CC(C=2N=CC=CC=2)=N1 NSFBBHBQTOEQBG-LJAQVGFWSA-N 0.000 claims description 2
- PMRGBQGHMSTEFL-QFIPXVFZSA-N n-[(2s)-2-amino-3-hydroxypropanoyl]-6-[2-(4-propan-2-ylphenyl)-5-pyridin-2-ylpyrazol-3-yl]hexanamide Chemical compound C1=CC(C(C)C)=CC=C1N1C(CCCCCC(=O)NC(=O)[C@@H](N)CO)=CC(C=2N=CC=CC=2)=N1 PMRGBQGHMSTEFL-QFIPXVFZSA-N 0.000 claims description 2
- CMMQJXFGOBKVCU-UHFFFAOYSA-N n-[1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-5-[2-(4-tert-butylphenyl)-5-pyridin-3-ylpyrazol-3-yl]pentanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCC(=O)NC(CC=2C=CC(O)=CC=2)C(N)=O)=CC(C=2C=NC=CC=2)=N1 CMMQJXFGOBKVCU-UHFFFAOYSA-N 0.000 claims description 2
- MCZJCTAHORPXHX-UHFFFAOYSA-N n-[2-amino-1-(4-hydroxyphenyl)-2-oxoethyl]-4-[2-(4-tert-butylphenyl)-5-pyridin-2-ylpyrazol-3-yl]benzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(C=2C=CC(=CC=2)C(=O)NC(C(N)=O)C=2C=CC(O)=CC=2)=CC(C=2N=CC=CC=2)=N1 MCZJCTAHORPXHX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 2
- ZDIDTRNIIIYXNA-MHZLTWQESA-N (2s)-2-amino-n-[3-[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]propyl]-3-(4-hydroxyphenyl)propanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCNC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=CN=CC=2)=N1 ZDIDTRNIIIYXNA-MHZLTWQESA-N 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- CSTNNNHMPXVIQQ-NDEPHWFRSA-N n-[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]-5-[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]pentanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=CN=CC=2)=N1 CSTNNNHMPXVIQQ-NDEPHWFRSA-N 0.000 claims 2
- NDXOHFMYRVKDNC-SANMLTNESA-N (2s)-2-amino-n-[3-[1-(4-tert-butylphenyl)-5-pyridin-3-ylpyrazol-3-yl]propanoyl]-3-(4-hydroxyphenyl)propanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(C=2C=NC=CC=2)=CC(CCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=N1 NDXOHFMYRVKDNC-SANMLTNESA-N 0.000 claims 1
- RYYTXUYWPXZEBE-SANMLTNESA-N (2s)-2-amino-n-[3-[2-(4-tert-butylphenyl)-5-pyridin-3-ylpyrazol-3-yl]propanoyl]-3-(4-hydroxyphenyl)propanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCC(=O)NC(=O)[C@@H](N)CC=2C=CC(O)=CC=2)=CC(C=2C=NC=CC=2)=N1 RYYTXUYWPXZEBE-SANMLTNESA-N 0.000 claims 1
- PKDWHPHPJUNING-NDEPHWFRSA-N (2s)-n-acetyl-2-amino-n-[3-[[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]amino]propyl]-3-(4-hydroxyphenyl)propanamide Chemical compound O=C([C@@H](N)CC=1C=CC(O)=CC=1)N(C(=O)C)CCCNC1=CC(C=2C=CN=CC=2)=NN1C1=CC=C(C(C)(C)C)C=C1 PKDWHPHPJUNING-NDEPHWFRSA-N 0.000 claims 1
- JBRGZRSDCVIDGP-NDEPHWFRSA-N 4-[(2s)-2-amino-3-[6-[2-(4-tert-butylphenyl)-5-pyridin-2-ylpyrazol-3-yl]hexanoylamino]-3-oxopropyl]benzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCCC(=O)NC(=O)[C@@H](N)CC=2C=CC(=CC=2)C(N)=O)=CC(C=2N=CC=CC=2)=N1 JBRGZRSDCVIDGP-NDEPHWFRSA-N 0.000 claims 1
- FZFDWNSNLNIDTC-UHFFFAOYSA-N 4-[2-[4-[[2-(4-tert-butylphenyl)-5-pyridin-4-ylpyrazol-3-yl]amino]butylamino]ethyl]phenol Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(NCCCCNCCC=2C=CC(O)=CC=2)=CC(C=2C=CN=CC=2)=N1 FZFDWNSNLNIDTC-UHFFFAOYSA-N 0.000 claims 1
- PJBPPDPPTKGSLG-RSXGOPAZSA-N 6-[2-(4-tert-butylphenyl)-5-pyridin-2-ylpyrazol-3-yl]-n-[(2s,3r)-2,3,4-trihydroxybutanoyl]hexanamide Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(CCCCCC(=O)NC(=O)[C@@H](O)[C@H](O)CO)=CC(C=2N=CC=CC=2)=N1 PJBPPDPPTKGSLG-RSXGOPAZSA-N 0.000 claims 1
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/06—Anabolic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Obesity (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32547001P | 2001-09-27 | 2001-09-27 | |
| US60/325,470 | 2001-09-27 | ||
| PCT/US2002/030801 WO2003026649A1 (en) | 2001-09-27 | 2002-09-27 | Methods of increasing endogenous testosterone levels |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2458661A1 true CA2458661A1 (en) | 2003-04-03 |
Family
ID=23268011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002458661A Abandoned CA2458661A1 (en) | 2001-09-27 | 2002-09-27 | Methods of increasing endogenous testosterone levels |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20040198799A1 (enExample) |
| EP (1) | EP1441724B8 (enExample) |
| JP (1) | JP2005504093A (enExample) |
| AT (1) | ATE372114T1 (enExample) |
| AU (1) | AU2002330120B2 (enExample) |
| CA (1) | CA2458661A1 (enExample) |
| DE (1) | DE60222286T2 (enExample) |
| DK (1) | DK1441724T3 (enExample) |
| ES (1) | ES2289143T3 (enExample) |
| IL (1) | IL161047A0 (enExample) |
| PT (1) | PT1441724E (enExample) |
| WO (1) | WO2003026649A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60112742T2 (de) * | 2000-05-19 | 2006-02-02 | Applied Research Systems Ars Holding N.V. | Verwendung von pyrazolderivaten zur behandlung von unfruchtbarkeit |
| AU2003265395A1 (en) * | 2002-08-14 | 2004-03-03 | Ppd Discovery, Inc. | Prenylation inhibitors and methods of their synthesis and use |
| US8492369B2 (en) | 2010-04-12 | 2013-07-23 | Clarus Therapeutics Inc | Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same |
| WO2006113505A2 (en) | 2005-04-15 | 2006-10-26 | Clarus Therapeutics, Inc. | Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same |
| WO2007002563A1 (en) | 2005-06-27 | 2007-01-04 | Exelixis, Inc. | Imidazole based lxr modulators |
| KR20090023562A (ko) | 2006-06-23 | 2009-03-05 | 제이-오일 밀스, 인코포레이티드 | 테스토스테론 증가제 |
| UY30892A1 (es) * | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| CA2750565C (en) * | 2009-01-30 | 2015-10-20 | Glaxosmithkline Llc | Crystalline n-{(1s)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1h-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride |
| WO2011161615A1 (en) | 2010-06-24 | 2011-12-29 | Ranbaxy Laboratories Limited | 5-lipoxygenase inhibitors |
| WO2011161645A1 (en) | 2010-06-25 | 2011-12-29 | Ranbaxy Laboratories Limited | 5-lipoxygenase inhibitors |
| WO2012003405A1 (en) | 2010-06-30 | 2012-01-05 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| NZ609955A (en) | 2010-11-09 | 2015-05-29 | Ironwood Pharmaceuticals Inc | Sgc stimulators |
| CN104066731B (zh) | 2011-12-27 | 2016-06-15 | 铁木医药有限公司 | 可用作sgc刺激剂的2-苄基、3-(嘧啶-2-基)取代的吡唑类 |
| US11564933B2 (en) | 2019-04-12 | 2023-01-31 | Tolmar, Inc. | Methods of treating testosterone deficiency |
| US20250171429A1 (en) * | 2022-02-23 | 2025-05-29 | Biohaven Therapeutics Ltd. | Pyrazolyl compounds as kv7 channel activators |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2665898B1 (fr) * | 1990-08-20 | 1994-03-11 | Sanofi | Derives d'amido-3 pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| DE4039733A1 (de) * | 1990-12-13 | 1992-06-17 | Basf Ag | Substituierte 5-aminopyrazole |
| CA2150703C (en) * | 1992-12-17 | 2002-01-08 | Pfizer Limited | Substituted pyrazoles |
| CN1174504A (zh) * | 1993-11-09 | 1998-02-25 | 麦克公司 | 促进生长激素释放的哌啶、吡咯烷和六氢－1h－吖庚因 |
| US5869688A (en) * | 1994-07-20 | 1999-02-09 | Monsanto Company | Preparation of substituted 3-aryl-5-haloalkyl-pyrazoles having herbicidal activity |
| JP2002502380A (ja) * | 1997-05-22 | 2002-01-22 | ジー．ディー．サール アンド カンパニー | ｐ３８キナーゼ阻害剤としてのピラゾール誘導体 |
| US6080763A (en) * | 1997-11-03 | 2000-06-27 | Boehringer Ingelheim Pharmaceuticals, Inc. | Aromatic heterocyclic compounds and their use as anti-inflammatory agents |
| CZ20013912A3 (cs) * | 1999-05-04 | 2002-05-15 | Strakan Limited | Androgen glykosid, sloučenina, testosteron-ß-D-glukosid, 5 alfa-Dihydrotestosteron- 17ß-D-glukosid, farmaceutický prostředek a pouľití sloučeniny |
| DE60112742T2 (de) * | 2000-05-19 | 2006-02-02 | Applied Research Systems Ars Holding N.V. | Verwendung von pyrazolderivaten zur behandlung von unfruchtbarkeit |
| NZ523656A (en) * | 2000-08-31 | 2004-11-26 | Pfizer Prod Inc | Pyrazole derivatives and their use as protein kinase inhibitors |
-
2002
- 2002-09-27 IL IL16104702A patent/IL161047A0/xx unknown
- 2002-09-27 WO PCT/US2002/030801 patent/WO2003026649A1/en not_active Ceased
- 2002-09-27 JP JP2003530286A patent/JP2005504093A/ja active Pending
- 2002-09-27 CA CA002458661A patent/CA2458661A1/en not_active Abandoned
- 2002-09-27 AT AT02766382T patent/ATE372114T1/de not_active IP Right Cessation
- 2002-09-27 AU AU2002330120A patent/AU2002330120B2/en not_active Ceased
- 2002-09-27 ES ES02766382T patent/ES2289143T3/es not_active Expired - Lifetime
- 2002-09-27 DK DK02766382T patent/DK1441724T3/da active
- 2002-09-27 EP EP02766382A patent/EP1441724B8/en not_active Expired - Lifetime
- 2002-09-27 US US10/489,863 patent/US20040198799A1/en not_active Abandoned
- 2002-09-27 DE DE60222286T patent/DE60222286T2/de not_active Expired - Fee Related
- 2002-09-27 PT PT02766382T patent/PT1441724E/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003026649A1 (en) | 2003-04-03 |
| PT1441724E (pt) | 2007-10-15 |
| AU2002330120B2 (en) | 2007-10-11 |
| EP1441724B8 (en) | 2007-10-17 |
| DK1441724T3 (da) | 2007-12-03 |
| ATE372114T1 (de) | 2007-09-15 |
| JP2005504093A (ja) | 2005-02-10 |
| US20040198799A1 (en) | 2004-10-07 |
| IL161047A0 (en) | 2004-08-31 |
| EP1441724B1 (en) | 2007-09-05 |
| ES2289143T3 (es) | 2008-02-01 |
| DE60222286D1 (de) | 2007-10-18 |
| EP1441724A1 (en) | 2004-08-04 |
| DE60222286T2 (de) | 2008-06-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |