CA2544857A1 - Vitamin d receptor modulators - Google Patents

Info

Publication number

CA2544857A1

CA2544857A1 CA002544857A CA2544857A CA2544857A1 CA 2544857 A1 CA2544857 A1 CA 2544857A1 CA 002544857 A CA002544857 A CA 002544857A CA 2544857 A CA2544857 A CA 2544857A CA 2544857 A1 CA2544857 A1 CA 2544857A1

Authority

CA

Canada

Prior art keywords

alkyl

nhc

ethyl

methyl

ch2ch2s

Prior art date

2003-11-20

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

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 102000009310 vitamin D receptors Human genes 0.000 title claims abstract description 49
• 108050000156 vitamin D receptors Proteins 0.000 title claims abstract description 49
• 150000001875 compounds Chemical class 0.000 claims abstract description 217
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 586
• 125000000217 alkyl group Chemical group 0.000 claims description 583
• -1 3-methyl-3-hydroxypentyl Chemical group 0.000 claims description 435
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 137
• 239000000203 mixture Substances 0.000 claims description 121
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 94
• DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 76
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 54
• 238000003556 assay Methods 0.000 claims description 53
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 50
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 50
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 49
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 49
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 48
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 44
• 238000011282 treatment Methods 0.000 claims description 40
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 37
• 239000001257 hydrogen Substances 0.000 claims description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 30
• 239000000651 prodrug Chemical class 0.000 claims description 28
• 229940002612 prodrug Drugs 0.000 claims description 28
• 238000000034 method Methods 0.000 claims description 27
• 150000002148 esters Chemical class 0.000 claims description 26
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 23
• 208000001132 Osteoporosis Diseases 0.000 claims description 23
• 150000002431 hydrogen Chemical group 0.000 claims description 23
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 22
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 19
• 238000009472 formulation Methods 0.000 claims description 19
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 17
• 208000037147 Hypercalcaemia Diseases 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000001475 halogen functional group Chemical group 0.000 claims description 17
• 230000000148 hypercalcaemia Effects 0.000 claims description 17
• 208000030915 hypercalcemia disease Diseases 0.000 claims description 17
• 239000004615 ingredient Substances 0.000 claims description 15
• 239000011734 sodium Substances 0.000 claims description 15
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 13
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 13
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 12
• 241000124008 Mammalia Species 0.000 claims description 11
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• 125000005647 linker group Chemical group 0.000 claims description 11
• 229940075993 receptor modulator Drugs 0.000 claims description 11
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
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• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 235000003351 Brassica cretica Nutrition 0.000 claims description 7
• 235000003343 Brassica rupestris Nutrition 0.000 claims description 7
• 229930003316 Vitamin D Natural products 0.000 claims description 7
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 7
• QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 235000010460 mustard Nutrition 0.000 claims description 7
• 229920006395 saturated elastomer Polymers 0.000 claims description 7
• 235000019166 vitamin D Nutrition 0.000 claims description 7
• 239000011710 vitamin D Substances 0.000 claims description 7
• 150000003710 vitamin D derivatives Chemical class 0.000 claims description 7
• 229940046008 vitamin d Drugs 0.000 claims description 7
• 241000219198 Brassica Species 0.000 claims description 6
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 6
• 206010060862 Prostate cancer Diseases 0.000 claims description 6
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• 125000002837 carbocyclic group Chemical group 0.000 claims description 6
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 6
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• 206010006187 Breast cancer Diseases 0.000 claims description 4
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• 208000013725 Chronic Kidney Disease-Mineral and Bone disease Diseases 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
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• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 4
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• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 4
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 4
• 206010039710 Scleroderma Diseases 0.000 claims description 4
• 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
• 206010052779 Transplant rejections Diseases 0.000 claims description 4
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
• 206010000496 acne Diseases 0.000 claims description 4
• 208000009621 actinic keratosis Diseases 0.000 claims description 4
• 231100000360 alopecia Toxicity 0.000 claims description 4
• 150000004663 bisphosphonates Chemical class 0.000 claims description 4
• 208000029742 colonic neoplasm Diseases 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
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• 102000055006 Calcitonin Human genes 0.000 claims description 3
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• 206010047642 Vitiligo Diseases 0.000 claims description 3
• 239000003098 androgen Substances 0.000 claims description 3
• 229940030486 androgens Drugs 0.000 claims description 3
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 3
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• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 3
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• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 12
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• 235000014347 soups Nutrition 0.000 claims 1
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• HXMZLDUBSSPQIB-UHFFFAOYSA-N 2-phenyl-1-benzofuran Chemical class O1C2=CC=CC=C2C=C1C1=CC=CC=C1 HXMZLDUBSSPQIB-UHFFFAOYSA-N 0.000 abstract description 2
• 230000000121 hypercalcemic effect Effects 0.000 abstract description 2
• GMRQFYUYWCNGIN-CLVAPQHMSA-N (5e)-5-[(2e)-2-[1-(6-hydroxy-6-methylheptan-2-yl)-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2\C1=C\C=C1/CC(O)CC(O)C1=C GMRQFYUYWCNGIN-CLVAPQHMSA-N 0.000 abstract 1
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