NZ530580A - Mediators of hedgehog signaling pathways, compositions and uses related thereto - Google Patents
Mediators of hedgehog signaling pathways, compositions and uses related theretoInfo
- Publication number
- NZ530580A NZ530580A NZ530580A NZ53058002A NZ530580A NZ 530580 A NZ530580 A NZ 530580A NZ 530580 A NZ530580 A NZ 530580A NZ 53058002 A NZ53058002 A NZ 53058002A NZ 530580 A NZ530580 A NZ 530580A
- Authority
- NZ
- New Zealand
- Prior art keywords
- aryl
- heteroaryl
- cycloalkyl
- heterocyclyl
- alkyl
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 8
- 230000008410 smoothened signaling pathway Effects 0.000 title description 3
- 210000004027 cell Anatomy 0.000 claims abstract description 101
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 42
- 230000037361 pathway Effects 0.000 claims abstract description 35
- 230000004913 activation Effects 0.000 claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 26
- 238000004519 manufacturing process Methods 0.000 claims abstract description 24
- 206010004146 Basal cell carcinoma Diseases 0.000 claims abstract description 22
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 241000289669 Erinaceus europaeus Species 0.000 claims abstract 39
- 201000011510 cancer Diseases 0.000 claims abstract 12
- 125000000217 alkyl group Chemical group 0.000 claims description 495
- 125000003118 aryl group Chemical group 0.000 claims description 331
- 125000001072 heteroaryl group Chemical group 0.000 claims description 325
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 285
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 282
- 125000000623 heterocyclic group Chemical group 0.000 claims description 249
- 125000003342 alkenyl group Chemical group 0.000 claims description 244
- -1 CF3) Chemical class 0.000 claims description 211
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 206
- 125000001424 substituent group Chemical group 0.000 claims description 188
- 125000003367 polycyclic group Chemical group 0.000 claims description 185
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 180
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 179
- 125000000304 alkynyl group Chemical group 0.000 claims description 141
- 229910052736 halogen Inorganic materials 0.000 claims description 131
- 150000002367 halogens Chemical class 0.000 claims description 131
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 124
- 125000004442 acylamino group Chemical group 0.000 claims description 121
- 125000003545 alkoxy group Chemical group 0.000 claims description 118
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 112
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 109
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 109
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 109
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 claims description 109
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 109
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 109
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 109
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 107
- 125000002252 acyl group Chemical group 0.000 claims description 106
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 106
- 150000007970 thio esters Chemical class 0.000 claims description 104
- 125000001931 aliphatic group Chemical group 0.000 claims description 103
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 103
- 125000004414 alkyl thio group Chemical group 0.000 claims description 103
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 103
- 125000002837 carbocyclic group Chemical group 0.000 claims description 103
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 103
- 150000002148 esters Chemical class 0.000 claims description 103
- ZORAAXQLJQXLOD-UHFFFAOYSA-N phosphonamidous acid Chemical compound NPO ZORAAXQLJQXLOD-UHFFFAOYSA-N 0.000 claims description 103
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 103
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 claims description 103
- AWIJRPNMLHPLNC-UHFFFAOYSA-N methanethioic s-acid Chemical compound SC=O AWIJRPNMLHPLNC-UHFFFAOYSA-N 0.000 claims description 102
- 150000008300 phosphoramidites Chemical class 0.000 claims description 102
- 125000003282 alkyl amino group Chemical group 0.000 claims description 100
- 125000003368 amide group Chemical group 0.000 claims description 97
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 97
- 150000002576 ketones Chemical class 0.000 claims description 97
- 125000003375 sulfoxide group Chemical group 0.000 claims description 97
- 239000004202 carbamide Substances 0.000 claims description 96
- 229910052760 oxygen Inorganic materials 0.000 claims description 95
- 229910052717 sulfur Inorganic materials 0.000 claims description 95
- 229910019142 PO4 Inorganic materials 0.000 claims description 91
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 91
- 239000010452 phosphate Substances 0.000 claims description 91
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 91
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 91
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 91
- 238000000034 method Methods 0.000 claims description 67
- 125000004122 cyclic group Chemical group 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 37
- 230000009459 hedgehog signaling Effects 0.000 claims description 24
- 230000033228 biological regulation Effects 0.000 claims description 23
- 239000002537 cosmetic Substances 0.000 claims description 17
- 230000001404 mediated effect Effects 0.000 claims description 15
- 230000019491 signal transduction Effects 0.000 claims description 13
- 238000000338 in vitro Methods 0.000 claims description 11
- 241000282414 Homo sapiens Species 0.000 claims description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 230000022159 cartilage development Effects 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 230000021595 spermatogenesis Effects 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 72
- WBTCZXYOKNRFQX-UHFFFAOYSA-N S1(=O)(=O)NC1=O Chemical group S1(=O)(=O)NC1=O WBTCZXYOKNRFQX-UHFFFAOYSA-N 0.000 claims 12
- 150000001409 amidines Chemical class 0.000 claims 12
- 150000001540 azides Chemical class 0.000 claims 12
- BSCOYGIDBGKPIX-UHFFFAOYSA-N diazenylphosphonic acid Chemical compound OP(O)(=O)N=N BSCOYGIDBGKPIX-UHFFFAOYSA-N 0.000 claims 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 12
- 208000009956 adenocarcinoma Diseases 0.000 claims 6
- 150000001408 amides Chemical class 0.000 claims 6
- 230000003779 hair growth Effects 0.000 claims 6
- 230000008470 skin growth Effects 0.000 claims 6
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 6
- 229940124530 sulfonamide Drugs 0.000 claims 6
- 150000003456 sulfonamides Chemical class 0.000 claims 6
- 208000000172 Medulloblastoma Diseases 0.000 claims 5
- 206010005003 Bladder cancer Diseases 0.000 claims 3
- 206010005949 Bone cancer Diseases 0.000 claims 3
- 208000018084 Bone neoplasm Diseases 0.000 claims 3
- 206010006187 Breast cancer Diseases 0.000 claims 3
- 208000026310 Breast neoplasm Diseases 0.000 claims 3
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 claims 3
- 201000009030 Carcinoma Diseases 0.000 claims 3
- 201000000274 Carcinosarcoma Diseases 0.000 claims 3
- 208000005243 Chondrosarcoma Diseases 0.000 claims 3
- 206010009944 Colon cancer Diseases 0.000 claims 3
- 208000006402 Ductal Carcinoma Diseases 0.000 claims 3
- 206010014967 Ependymoma Diseases 0.000 claims 3
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 3
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims 3
- 208000032612 Glial tumor Diseases 0.000 claims 3
- 206010018338 Glioma Diseases 0.000 claims 3
- 208000005016 Intestinal Neoplasms Diseases 0.000 claims 3
- 206010023347 Keratoacanthoma Diseases 0.000 claims 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 3
- 208000000265 Lobular Carcinoma Diseases 0.000 claims 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 3
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 claims 3
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims 3
- 206010029260 Neuroblastoma Diseases 0.000 claims 3
- 208000009277 Neuroectodermal Tumors Diseases 0.000 claims 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 3
- 206010060862 Prostate cancer Diseases 0.000 claims 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 3
- 206010038389 Renal cancer Diseases 0.000 claims 3
- 208000006265 Renal cell carcinoma Diseases 0.000 claims 3
- 201000000582 Retinoblastoma Diseases 0.000 claims 3
- 206010039491 Sarcoma Diseases 0.000 claims 3
- 208000000453 Skin Neoplasms Diseases 0.000 claims 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 3
- 208000033781 Thyroid carcinoma Diseases 0.000 claims 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 3
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims 3
- 206010046392 Ureteric cancer Diseases 0.000 claims 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 3
- 208000008385 Urogenital Neoplasms Diseases 0.000 claims 3
- 208000002517 adenoid cystic carcinoma Diseases 0.000 claims 3
- 201000005188 adrenal gland cancer Diseases 0.000 claims 3
- 208000024447 adrenal gland neoplasm Diseases 0.000 claims 3
- 201000003714 breast lobular carcinoma Diseases 0.000 claims 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- 208000029742 colonic neoplasm Diseases 0.000 claims 3
- 206010017758 gastric cancer Diseases 0.000 claims 3
- 208000005017 glioblastoma Diseases 0.000 claims 3
- 201000011066 hemangioma Diseases 0.000 claims 3
- 206010020718 hyperplasia Diseases 0.000 claims 3
- 201000002313 intestinal cancer Diseases 0.000 claims 3
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 claims 3
- 201000010982 kidney cancer Diseases 0.000 claims 3
- 201000005202 lung cancer Diseases 0.000 claims 3
- 208000020816 lung neoplasm Diseases 0.000 claims 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 3
- 206010027191 meningioma Diseases 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 201000011216 nasopharynx carcinoma Diseases 0.000 claims 3
- 201000008968 osteosarcoma Diseases 0.000 claims 3
- 201000002528 pancreatic cancer Diseases 0.000 claims 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 3
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims 3
- 201000000849 skin cancer Diseases 0.000 claims 3
- 208000000649 small cell carcinoma Diseases 0.000 claims 3
- 201000011549 stomach cancer Diseases 0.000 claims 3
- 201000002510 thyroid cancer Diseases 0.000 claims 3
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims 3
- 201000007423 tubular adenocarcinoma Diseases 0.000 claims 3
- 201000011294 ureter cancer Diseases 0.000 claims 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims 3
- 208000037964 urogenital cancer Diseases 0.000 claims 3
- 210000001647 gastrula Anatomy 0.000 claims 2
- 230000003394 haemopoietic effect Effects 0.000 claims 2
- 210000004185 liver Anatomy 0.000 claims 2
- 230000001537 neural effect Effects 0.000 claims 2
- RLBIQVVOMOPOHC-UHFFFAOYSA-N parathion-methyl Chemical compound COP(=S)(OC)OC1=CC=C([N+]([O-])=O)C=C1 RLBIQVVOMOPOHC-UHFFFAOYSA-N 0.000 claims 2
- 230000008439 repair process Effects 0.000 claims 2
- 210000002460 smooth muscle Anatomy 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 244000060234 Gmelina philippensis Species 0.000 description 32
- 150000001299 aldehydes Chemical class 0.000 description 31
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 31
- 101100203200 Danio rerio shha gene Proteins 0.000 description 29
- 101150088976 shh gene Proteins 0.000 description 29
- 108090000623 proteins and genes Proteins 0.000 description 27
- 238000011161 development Methods 0.000 description 17
- 230000018109 developmental process Effects 0.000 description 17
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 15
- 108010069873 Patched Receptors Proteins 0.000 description 14
- 102000000017 Patched Receptors Human genes 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 230000006698 induction Effects 0.000 description 9
- 238000000059 patterning Methods 0.000 description 8
- 108700028369 Alleles Proteins 0.000 description 7
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 7
- 102000003693 Hedgehog Proteins Human genes 0.000 description 7
- 108090000031 Hedgehog Proteins Proteins 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 230000035772 mutation Effects 0.000 description 6
- 210000003458 notochord Anatomy 0.000 description 6
- 206010062804 Basal cell naevus syndrome Diseases 0.000 description 5
- 208000031995 Gorlin syndrome Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 210000001612 chondrocyte Anatomy 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 201000005734 nevoid basal cell carcinoma syndrome Diseases 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 210000002023 somite Anatomy 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000013020 embryo development Effects 0.000 description 4
- 210000002161 motor neuron Anatomy 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 241000251468 Actinopterygii Species 0.000 description 3
- 101150061927 BMP2 gene Proteins 0.000 description 3
- 241000252212 Danio rerio Species 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 210000000982 limb bud Anatomy 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 101800001415 Bri23 peptide Proteins 0.000 description 2
- 101800000655 C-terminal peptide Proteins 0.000 description 2
- 102400000107 C-terminal peptide Human genes 0.000 description 2
- 241000051107 Paraechinus aethiopicus Species 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108050003627 Wnt Proteins 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000008614 cellular interaction Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 210000001259 mesencephalon Anatomy 0.000 description 2
- 210000003716 mesoderm Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000008189 vertebrate development Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 241001455272 Amniota Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 101100518995 Caenorhabditis elegans pax-3 gene Proteins 0.000 description 1
- 206010061764 Chromosomal deletion Diseases 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108700029231 Developmental Genes Proteins 0.000 description 1
- 108700018846 Drosophila hh Proteins 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 101000606317 Drosophila melanogaster Protein patched Proteins 0.000 description 1
- 108700030338 Drosophila wg Proteins 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 description 1
- 238000005588 Kraus reaction Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 101100518997 Mus musculus Pax3 gene Proteins 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 201000010829 Spina bifida Diseases 0.000 description 1
- 208000006097 Spinal Dysraphism Diseases 0.000 description 1
- 241000255588 Tephritidae Species 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 108010016200 Zinc Finger Protein GLI1 Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000468 autoproteolytic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 101150067309 bmp4 gene Proteins 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000002648 chondrogenic effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000009547 development abnormality Effects 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000007045 gastrulation Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 210000003559 hypertrophic chondrocyte Anatomy 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000035992 intercellular communication Effects 0.000 description 1
- 230000007653 larval development Effects 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000001002 morphogenetic effect Effects 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 210000001020 neural plate Anatomy 0.000 description 1
- 210000000276 neural tube Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 230000007261 regionalization Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000001202 rhombencephalon Anatomy 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 210000002356 skeleton Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000037426 transcriptional repression Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
-
- 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Cosmetics (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Liquid Crystal Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30844901P | 2001-07-27 | 2001-07-27 | |
| US33803101P | 2001-11-13 | 2001-11-13 | |
| PCT/US2002/024073 WO2003011219A2 (en) | 2001-07-27 | 2002-07-29 | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ530580A true NZ530580A (en) | 2007-02-23 |
Family
ID=26976260
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ530580A NZ530580A (en) | 2001-07-27 | 2002-07-29 | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US8354397B2 (enExample) |
| EP (1) | EP1482928B1 (enExample) |
| JP (1) | JP4658473B2 (enExample) |
| KR (1) | KR20040031782A (enExample) |
| CN (1) | CN1638765A (enExample) |
| AT (1) | ATE443518T1 (enExample) |
| AU (1) | AU2002327390B2 (enExample) |
| BR (1) | BR0211513A (enExample) |
| CA (1) | CA2455100C (enExample) |
| DE (1) | DE60233823D1 (enExample) |
| EA (1) | EA007339B1 (enExample) |
| IL (1) | IL159858A0 (enExample) |
| MX (1) | MXPA04000803A (enExample) |
| NO (1) | NO20040342L (enExample) |
| NZ (1) | NZ530580A (enExample) |
| PL (1) | PL366799A1 (enExample) |
| WO (1) | WO2003011219A2 (enExample) |
Families Citing this family (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69841320D1 (de) | 1997-02-10 | 2010-01-07 | Harvard College | Verfahren zur modulation von hämatopoese und vaskulärem wachstum |
| US6984522B2 (en) | 2000-08-03 | 2006-01-10 | Regents Of The University Of Michigan | Isolation and use of solid tumor stem cells |
| US8044259B2 (en) | 2000-08-03 | 2011-10-25 | The Regents Of The University Of Michigan | Determining the capability of a test compound to affect solid tumor stem cells |
| DK1387674T3 (en) | 2000-10-13 | 2017-04-10 | Curis Inc | Hedgehog antagonists, methods and uses related thereto |
| US7708998B2 (en) | 2000-10-13 | 2010-05-04 | Curis, Inc. | Methods of inhibiting unwanted cell proliferation using hedgehog antagonists |
| TW200304820A (en) * | 2002-03-25 | 2003-10-16 | Avanir Pharmaceuticals | Use of benzimidazole analogs in the treatment of cell proliferation |
| CN100381437C (zh) | 2002-04-17 | 2008-04-16 | 赛特凯恩蒂克公司 | 化合物、组合物和方法 |
| ATE404200T1 (de) * | 2002-04-22 | 2008-08-15 | Univ Johns Hopkins Med | Modulatoren von hedgehog signalpfaden, zusammensetzungen und verwandte verwendungen |
| DE60326248D1 (de) | 2002-07-17 | 2009-04-02 | Cytokinetics Inc | Verbindungen, zusammensetzungen und verfahren zur behandlung von zellulären proliferativen erkrankungen |
| TWI276631B (en) * | 2002-09-12 | 2007-03-21 | Avanir Pharmaceuticals | Phenyl-aza-benzimidazole compounds for modulating IgE and inhibiting cellular proliferation |
| DE602004006852D1 (de) | 2003-04-17 | 2007-07-19 | Janssen Pharmaceutica Nv | 2-phenyl-benzimidazol und 2-phenyl-imidazo-4,5ü-pyridin-derivate als checkpoint-kinase-cds1 (chk2)-hemmer zur behandlung von krebs |
| WO2005030206A1 (en) * | 2003-09-24 | 2005-04-07 | Imclone Systems Incorporated | Aryl-1,3-azole derivatives and methods for inhibiting heparnase activity |
| EP1730280B1 (en) | 2004-03-26 | 2018-10-24 | Curis, Inc. | Rna interference modulators of hedgehog signaling and uses thereof |
| DE602005027739D1 (de) | 2004-06-30 | 2011-06-09 | Janssen Pharmaceutica Nv | Arylsubstituiertes benzimidazol- und imidazopyridinether als wirkstoffe gegen krebs |
| KR20160058972A (ko) | 2004-09-02 | 2016-05-25 | 제넨테크, 인크. | 헤지호그 신호전달에 대한 피리딜 억제제 |
| CA2587489C (en) * | 2004-11-03 | 2013-12-31 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| JP2008535790A (ja) * | 2005-03-03 | 2008-09-04 | サートリス ファーマシューティカルズ, インコーポレイテッド | サーチュインモジュレーターであるn−フェニルベンズアミド誘導体 |
| WO2006094246A2 (en) * | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | N-arylmethyl benzamide sirtuin modulators |
| WO2006124780A2 (en) * | 2005-05-12 | 2006-11-23 | Kalypsys, Inc. | Ih-benzo [d] imidazole compounds as inhibitors of b-raf kinase |
| US8088928B2 (en) * | 2005-08-04 | 2012-01-03 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8093401B2 (en) * | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US7855289B2 (en) | 2005-08-04 | 2010-12-21 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| AU2006278504B2 (en) * | 2005-08-04 | 2013-01-17 | Sirtris Pharmaceuticals, Inc. | Imidazopyridine derivatives as sirtuin modulating agents |
| AU2006308847C1 (en) | 2005-10-31 | 2012-05-10 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for treating and diagnosing cancer |
| US7625759B2 (en) | 2005-12-19 | 2009-12-01 | Genentech, Inc. | Method for using BOC/CDO to modulate hedgehog signaling |
| WO2008121102A2 (en) * | 2006-02-21 | 2008-10-09 | The Regents Of The University Of Michigan | Hedgehog signaling pathway antagonist cancer treatment |
| EP2614839A3 (en) | 2006-04-05 | 2015-01-28 | Genentech, Inc. | Method for using BOC/CDO to modulate hedgehog signaling |
| MY181496A (en) * | 2006-10-31 | 2020-12-23 | Government Of The United States Of America Represented By The Sec Dep Of Health And Human Services | Smoothened polypeptides and methods of use |
| JP2010513263A (ja) * | 2006-12-15 | 2010-04-30 | ファイザー・プロダクツ・インク | ベンズイミダゾール誘導体 |
| TWI433674B (zh) | 2006-12-28 | 2014-04-11 | Infinity Discovery Inc | 環杷明(cyclopamine)類似物類 |
| EP2106439B1 (en) | 2007-01-24 | 2014-11-12 | The Regents of the University of Michigan | Compositions and methods for treating and diagnosing pancreatic cancer |
| TW200918542A (en) | 2007-06-20 | 2009-05-01 | Sirtris Pharmaceuticals Inc | Sirtuin modulating compounds |
| CL2008001822A1 (es) * | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de tiazolo[5,4-b]piridina; composicion farmaceutica que comprende a dichos compuestos; y uso del compuesto en el tratamiento de la resistencia a la insulina, sindrome metabolico, diabetes, entre otras. |
| ME00962B (me) * | 2007-06-29 | 2012-06-20 | Pfizer | Benzimidazolski derivati |
| AU2008319267A1 (en) * | 2007-11-01 | 2009-05-07 | Sirtris Pharmaceuticals, Inc. | Amide derivatives as sirtuin modulators |
| EP2217606A1 (en) * | 2007-11-08 | 2010-08-18 | Sirtris Pharmaceuticals, Inc. | Solubilized thiazolopyridines |
| EP3190121B1 (en) | 2007-12-27 | 2019-02-20 | Infinity Pharmaceuticals, Inc. | Methods for stereoselective reduction of cyclopamine 4-en-3-one derivative |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| FR2930552B1 (fr) | 2008-04-24 | 2012-10-12 | Centre Nat Rech Scient | N-acylthiourees et n-acylurees inhibiteurs de la voie de signalisation des proteines hedgehog |
| WO2010021381A1 (ja) * | 2008-08-22 | 2010-02-25 | 武田薬品工業株式会社 | 縮合複素環誘導体およびその用途 |
| AU2009299927B2 (en) * | 2008-10-01 | 2013-05-30 | Novartis Ag | Smoothened antagonism for the treatment of hedgehog pathway-related disorders |
| CN102388054B (zh) | 2008-12-19 | 2015-03-04 | 西特里斯药业公司 | 噻唑并吡啶沉默调节蛋白调节剂的化合物 |
| MX2011013294A (es) * | 2009-06-11 | 2012-01-12 | Siena Biotech Spa | Antagonistas de la trayectoria de hedgehog y aplicaciones terapeuticas de los mismos. |
| AR077014A1 (es) * | 2009-06-19 | 2011-07-27 | Lilly Co Eli | Compuesto derivado de ftalazina 1,4-disustituida, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para el tratamiento de cancer |
| FR2948367A1 (fr) * | 2009-07-24 | 2011-01-28 | Centre Nat Rech Scient | Derives d'acyl-guanidines modulateurs de la voie de signalisation des proteines hedgehog |
| WO2011017551A1 (en) | 2009-08-05 | 2011-02-10 | Infinity Pharmaceuticals, Inc. | Enzymatic transamination of cyclopamine analogs |
| SG178873A1 (en) | 2009-08-25 | 2012-04-27 | Abraxis Bioscience Llc | Combination therapy with nanoparticle compositions of taxane and hedgehog inhibitors |
| EP2571357B1 (en) | 2010-05-21 | 2016-07-06 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| WO2012037217A1 (en) | 2010-09-14 | 2012-03-22 | Infinity Pharmaceuticals, Inc. | Transfer hydrogenation of cyclopamine analogs |
| CN103298474B (zh) | 2010-11-10 | 2016-06-29 | 无限药品股份有限公司 | 杂环化合物及其用途 |
| TWI617559B (zh) * | 2010-12-22 | 2018-03-11 | 江蘇恆瑞醫藥股份有限公司 | 2-芳基咪唑并[1,2-b]嗒.2-苯基咪唑并[1,2-a]吡啶,和2-苯基咪唑并[1,2-a]吡衍生物 |
| US9708299B2 (en) | 2011-01-03 | 2017-07-18 | Genentech, Inc. | Hedgehog antagonists having zinc binding moieties |
| TWI546305B (zh) | 2011-01-10 | 2016-08-21 | 英菲尼提製藥股份有限公司 | 製備異喹啉酮之方法及異喹啉酮之固體形式 |
| WO2013012918A1 (en) | 2011-07-19 | 2013-01-24 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| AU2012284088B2 (en) | 2011-07-19 | 2015-10-08 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| CA2846431A1 (en) | 2011-08-29 | 2013-03-07 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| US9630979B2 (en) | 2011-09-29 | 2017-04-25 | Infinity Pharmaceuticals, Inc. | Inhibitors of monoacylglycerol lipase and methods of their use |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN103570625A (zh) * | 2012-07-19 | 2014-02-12 | 南京英派药业有限公司 | N-(3-杂芳基芳基)-4-芳基芳基甲酰胺和类似物作为Hedgehog通路抑制剂及其应用 |
| CN105102000B (zh) | 2012-11-01 | 2021-10-22 | 无限药品公司 | 使用pi3激酶亚型调节剂的癌症疗法 |
| AU2013352256A1 (en) | 2012-11-29 | 2015-06-18 | Strasspharma, Llc | Methods of modulating follicle stimulating hormone activity |
| WO2014151630A2 (en) * | 2013-03-15 | 2014-09-25 | Irm Llc | Compounds and compositions for the treatment of parasitic diseases |
| US9296754B2 (en) | 2013-03-15 | 2016-03-29 | Novartis Ag | Compounds and compositions for the treatment of parasitic diseases |
| EP2970194A1 (en) | 2013-03-15 | 2016-01-20 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| WO2014151729A1 (en) | 2013-03-15 | 2014-09-25 | Irm Llc | Compounds and compositions for the treatment of parasitic diseases |
| US9192609B2 (en) | 2013-04-17 | 2015-11-24 | Hedgepath Pharmaceuticals, Inc. | Treatment and prognostic monitoring of proliferation disorders using hedgehog pathway inhibitors |
| SG10201709926VA (en) | 2013-05-30 | 2017-12-28 | Infinity Pharmaceuticals Inc | Treatment of cancers using pi3 kinase isoform modulators |
| WO2015036405A1 (en) | 2013-09-10 | 2015-03-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for diagnosing and treating basal cell carcinoma |
| MX389256B (es) | 2013-10-04 | 2025-03-20 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos. |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2015061204A1 (en) | 2013-10-21 | 2015-04-30 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US9814703B2 (en) | 2013-11-14 | 2017-11-14 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for treating cancer by activation of BMP signaling |
| HRP20182021T1 (hr) | 2013-12-19 | 2019-01-25 | Novartis Ag | Derivati [1,2,4]triazolo[1,5-a]pirimidina kao inhibitori proteazoma protozoe za liječenje parazitskih bolesti poput lišmenijaze |
| EA201691872A1 (ru) | 2014-03-19 | 2017-04-28 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения для применения в лечении pi3k-гамма-опосредованных расстройств |
| US20150320754A1 (en) | 2014-04-16 | 2015-11-12 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| WO2015168079A1 (en) | 2014-04-29 | 2015-11-05 | Infinity Pharmaceuticals, Inc. | Pyrimidine or pyridine derivatives useful as pi3k inhibitors |
| CN104151250B (zh) * | 2014-07-22 | 2016-08-31 | 大连理工大学 | 一类含苯并咪唑基团的二芳基酰胺类化合物及其合成和应用 |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| BR112017026103B1 (pt) | 2015-06-04 | 2023-10-03 | Sol-Gel Technologies Ltd | Composições tópicas com composto inibidor de hedgehog, sistema de entrega tópica e seus usos |
| TW201713650A (en) * | 2015-06-22 | 2017-04-16 | Actelion Pharmaceuticals Ltd | NADPH oxidase 4 inhibitors |
| CN108349985A (zh) | 2015-09-14 | 2018-07-31 | 无限药品股份有限公司 | 异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法 |
| WO2017139497A1 (en) | 2016-02-11 | 2017-08-17 | PellePharm, Inc. | Hedgehog inhibitor for use in relief of and treatment of pruritus or itching |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP3474856B1 (en) | 2016-06-24 | 2022-09-14 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| US10767164B2 (en) | 2017-03-30 | 2020-09-08 | The Research Foundation For The State University Of New York | Microenvironments for self-assembly of islet organoids from stem cells differentiation |
| CN107056723A (zh) * | 2017-04-21 | 2017-08-18 | 云南大学 | 一种具有抑制血管内皮生长因子受体信号传导的化合物 |
| WO2018211007A1 (en) * | 2017-05-18 | 2018-11-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of mast cell diseases |
| CN112511569B (zh) * | 2021-02-07 | 2021-05-11 | 杭州筋斗腾云科技有限公司 | 网络资源访问请求的处理方法、系统及计算机设备 |
| CN115477615B (zh) * | 2022-10-17 | 2024-06-18 | 黄山学院 | N-(3-(苯并咪唑-2-基)苯基)酰胺类化合物及其制备方法和应用 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3164603A (en) * | 1965-01-05 | xnhcox | ||
| DE883284C (de) | 1938-11-27 | 1953-07-16 | Hoechst Ag | Verfahren zur Erzeugung von Azofarbstoffen auf Gebilden aus synthetischen hoehermolekularen Polyamidverbindungen oder auf Faser-gemischen, die Faserstoffe aus den Polyamidverbindungen enthalten |
| FR998985A (enExample) * | 1948-11-09 | 1952-01-24 | ||
| US2547307A (en) * | 1948-11-09 | 1951-04-03 | Gen Aniline & Film Corp | Yellow diffusion-fast color formers of the benzimidazole class |
| US2768894A (en) * | 1954-04-30 | 1956-10-30 | Gen Aniline & Film Corp | Photographic element with emulsion layer containing color former and wetting agent |
| DE1079762B (de) * | 1955-09-07 | 1960-04-14 | Bayer Ag | Verfahren zur Herstellung von Kuepenfarbstoffen der Thiazol- und Oxazolreihe |
| DE1282821B (de) | 1960-07-15 | 1968-11-14 | Natmar Inc | Fluoreszierende Markierungsmittel |
| US3162642A (en) * | 1960-07-15 | 1964-12-22 | Nat Marking Mach Co | Fluorescent pigments |
| US5641764A (en) * | 1989-03-31 | 1997-06-24 | Peter Maccallum Institute | Halogenated DNA ligand radiosensitizers for cancer therapy |
| CH685875A5 (fr) | 1991-04-26 | 1995-10-31 | Pierre Baudet | Les N-phényl-benzamides protecteurs contre les effets nocifs de la lumière ultra-violette |
| US5277839A (en) * | 1992-06-03 | 1994-01-11 | Litton Industrial Automation Automated Vehicles | Guidepath material |
| EP0672031B1 (en) | 1992-12-02 | 2003-03-12 | Pfizer Inc. | Catechol diethers as selective pde iv inhibitors |
| JP3015998B2 (ja) * | 1993-08-31 | 2000-03-06 | キヤノン株式会社 | 液晶性化合物、それを含む液晶組成物、該液晶組成物を用いた液晶素子、液晶装置、並びに表示方法 |
| US5496826A (en) * | 1994-09-02 | 1996-03-05 | Bristol-Myers Squibb Company | Pharmaceutical methods of using heterocyclic derivatives of N-phenylamides |
| US5563143A (en) | 1994-09-21 | 1996-10-08 | Pfizer Inc. | Catechol diether compounds as inhibitors of TNF release |
| US5821258A (en) * | 1994-12-27 | 1998-10-13 | Mitsui Chemicals, Inc. | Phenylbenzimidazole derivatives |
| JP3223090B2 (ja) * | 1994-12-27 | 2001-10-29 | 三井化学株式会社 | フェニルベンズイミダゾール誘導体 |
| GB9503946D0 (en) * | 1995-02-28 | 1995-04-19 | Cancer Res Campaign Tech | Benzazole compounds |
| WO1998017267A1 (en) * | 1996-10-23 | 1998-04-30 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| WO1998027108A2 (en) | 1996-12-16 | 1998-06-25 | Fujisawa Pharmaceutical Co., Ltd. | New amide compounds and their use as nitric oxide synthase inhibitors |
| US5994394A (en) * | 1997-03-21 | 1999-11-30 | Industrial Technology Research Institute | Polyheterocyclic compounds |
| US6649631B1 (en) * | 1997-10-23 | 2003-11-18 | The Board Of Regents Of The University Of Texas System | Compositions and methods for treating bone deficit conditions |
| US6046229A (en) * | 1998-01-06 | 2000-04-04 | Industrial Technology Research Institute | Polyaryl antitumor agents |
| US6303645B1 (en) * | 1998-05-22 | 2001-10-16 | Avanir Pharmaceuticals | Benzimidazole derivatives as modulators of IgE |
| CZ20004351A3 (cs) * | 1998-05-22 | 2001-10-17 | Avanir Pharmaceuticals | Benzimidazolová analoga pro sniľování hladiny IgE |
| US6919366B2 (en) * | 1998-05-22 | 2005-07-19 | Avanir Pharmaceuticals | Benzimidazole derivatives as modulators of IgE |
| IL139811A0 (en) | 1998-06-04 | 2002-02-10 | Abbott Lab | Cell adhesion-inhibiting antinflammatory compounds |
| PL349192A1 (en) | 1998-12-18 | 2002-07-01 | Axys Pharmaceuticals | Protease inhibitors |
| US6291516B1 (en) * | 1999-01-13 | 2001-09-18 | Curis, Inc. | Regulators of the hedgehog pathway, compositions and uses related thereto |
| WO2001019800A2 (en) * | 1999-09-16 | 2001-03-22 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| GB0007934D0 (en) * | 2000-03-31 | 2000-05-17 | Darwin Discovery Ltd | Chemical compounds |
| MXPA02010763A (es) * | 2000-06-14 | 2003-03-10 | Warner Lambert Co | Heterociclicos biciclos-6,5 fusionados. |
| ES2291455T3 (es) * | 2001-03-12 | 2008-03-01 | Avanir Pharmaceuticals | Compuestos de bencimidazol para modular ige e inhibir la proliferacion celular. |
| CA2587489C (en) * | 2004-11-03 | 2013-12-31 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
-
2002
- 2002-07-29 EA EA200400080A patent/EA007339B1/ru not_active IP Right Cessation
- 2002-07-29 MX MXPA04000803A patent/MXPA04000803A/es not_active Application Discontinuation
- 2002-07-29 NZ NZ530580A patent/NZ530580A/en unknown
- 2002-07-29 JP JP2003516451A patent/JP4658473B2/ja not_active Expired - Fee Related
- 2002-07-29 CN CNA028186796A patent/CN1638765A/zh active Pending
- 2002-07-29 IL IL15985802A patent/IL159858A0/xx unknown
- 2002-07-29 AU AU2002327390A patent/AU2002327390B2/en not_active Ceased
- 2002-07-29 DE DE60233823T patent/DE60233823D1/de not_active Expired - Lifetime
- 2002-07-29 EP EP02763383A patent/EP1482928B1/en not_active Expired - Lifetime
- 2002-07-29 PL PL02366799A patent/PL366799A1/xx not_active Application Discontinuation
- 2002-07-29 CA CA2455100A patent/CA2455100C/en not_active Expired - Fee Related
- 2002-07-29 WO PCT/US2002/024073 patent/WO2003011219A2/en not_active Ceased
- 2002-07-29 KR KR10-2004-7001176A patent/KR20040031782A/ko not_active Ceased
- 2002-07-29 BR BR0211513-1A patent/BR0211513A/pt not_active IP Right Cessation
- 2002-07-29 US US10/484,945 patent/US8354397B2/en not_active Expired - Fee Related
- 2002-07-29 AT AT02763383T patent/ATE443518T1/de not_active IP Right Cessation
-
2004
- 2004-01-26 NO NO20040342A patent/NO20040342L/no not_active Application Discontinuation
-
2012
- 2012-12-12 US US13/712,525 patent/US8772275B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP4658473B2 (ja) | 2011-03-23 |
| IL159858A0 (en) | 2004-06-20 |
| AU2002327390B2 (en) | 2008-06-26 |
| PL366799A1 (en) | 2005-02-07 |
| US20130190350A1 (en) | 2013-07-25 |
| CA2455100C (en) | 2013-05-28 |
| US8772275B2 (en) | 2014-07-08 |
| US20050085519A1 (en) | 2005-04-21 |
| EP1482928A2 (en) | 2004-12-08 |
| KR20040031782A (ko) | 2004-04-13 |
| JP2005507860A (ja) | 2005-03-24 |
| EA200400080A1 (ru) | 2005-02-24 |
| WO2003011219A2 (en) | 2003-02-13 |
| NO20040342L (no) | 2004-03-26 |
| ATE443518T1 (de) | 2009-10-15 |
| EP1482928A4 (en) | 2005-10-12 |
| DE60233823D1 (de) | 2009-11-05 |
| EP1482928B1 (en) | 2009-09-23 |
| CN1638765A (zh) | 2005-07-13 |
| WO2003011219A3 (en) | 2004-09-23 |
| BR0211513A (pt) | 2005-08-30 |
| MXPA04000803A (es) | 2004-05-21 |
| CA2455100A1 (en) | 2003-02-13 |
| US8354397B2 (en) | 2013-01-15 |
| EA007339B1 (ru) | 2006-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2002327390B2 (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto | |
| AU2003231032B2 (en) | Modulators of hedgehog signaling pathways, compositions and uses related thereto | |
| US9173869B2 (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto | |
| CA2385736C (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto | |
| AU2002327390A1 (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto | |
| AU780612C (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto | |
| US7300929B2 (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto | |
| US20050080138A1 (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto | |
| ZA200400582B (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto. | |
| AU2011224045A1 (en) | Modulators of hedgehog signaling pathways, compositions and uses related thereto | |
| EP1326600A2 (en) | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) |