CA2537883A1

CA2537883A1 - Substituted bicyclic quinazolin-4-ylamine derivatives

Substituted bicyclic quinazolin-4-ylamine derivatives Download PDF

Info

Publication number: CA2537883A1
Authority: CA; Canada
Prior art keywords: compound; pyridin; c6alkyl; pharmaceutically acceptable; pyrido
Prior art date: 2003-09-09
Legal status : Abandoned

Application number

CA002537883A

Other languages

English (en)

French (fr)

Inventor

Rajagopal Bakthavatchalam

Charles A. Blum

Bertrand L. Chenard

Current Assignee

Neurogen Corp

Original Assignee

Individual

Priority date

2003-09-09

Filing date

2004-09-09

Publication date

2005-03-17

2004-09-09 Application filed by Individual filed Critical Individual

2005-03-17 Publication of CA2537883A1 publication Critical patent/CA2537883A1/en

Status Abandoned legal-status Critical Current

Links

-1 bicyclic quinazolin-4-ylamine derivatives Chemical class 0.000 title claims abstract description 159
150000001875 compounds Chemical class 0.000 claims abstract description 338
238000000034 method Methods 0.000 claims abstract description 75
230000000694 effects Effects 0.000 claims abstract description 60
239000003446 ligand Substances 0.000 claims abstract description 37
241001465754 Metazoa Species 0.000 claims abstract description 35
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
238000000338 in vitro Methods 0.000 claims abstract description 14
238000001727 in vivo Methods 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims description 106
208000002193 Pain Diseases 0.000 claims description 101
125000001424 substituent group Chemical group 0.000 claims description 97
108010062740 TRPV Cation Channels Proteins 0.000 claims description 96
102000011040 TRPV Cation Channels Human genes 0.000 claims description 95
230000036407 pain Effects 0.000 claims description 89
239000000203 mixture Substances 0.000 claims description 79
125000000623 heterocyclic group Chemical group 0.000 claims description 75
210000004027 cell Anatomy 0.000 claims description 73
YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 claims description 68
238000003556 assay Methods 0.000 claims description 61
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 60
229910052736 halogen Inorganic materials 0.000 claims description 54
229910052739 hydrogen Inorganic materials 0.000 claims description 54
150000002367 halogens Chemical class 0.000 claims description 53
239000001257 hydrogen Substances 0.000 claims description 53
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 47
238000009739 binding Methods 0.000 claims description 43
230000027455 binding Effects 0.000 claims description 41
229960002504 capsaicin Drugs 0.000 claims description 32
235000017663 capsaicin Nutrition 0.000 claims description 32
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
229910052757 nitrogen Inorganic materials 0.000 claims description 29
239000000556 agonist Substances 0.000 claims description 27
208000004296 neuralgia Diseases 0.000 claims description 27
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 23
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 18
229910052760 oxygen Inorganic materials 0.000 claims description 18
208000003251 Pruritus Diseases 0.000 claims description 17
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
241000282414 Homo sapiens Species 0.000 claims description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
229910052717 sulfur Inorganic materials 0.000 claims description 14
208000021722 neuropathic pain Diseases 0.000 claims description 13
125000004043 oxo group Chemical group O=* 0.000 claims description 13
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 12
239000011575 calcium Substances 0.000 claims description 12
229910052791 calcium Inorganic materials 0.000 claims description 12
230000027425 release of sequestered calcium ion into cytosol Effects 0.000 claims description 12
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 11
125000003118 aryl group Chemical group 0.000 claims description 11
239000000546 pharmaceutical excipient Substances 0.000 claims description 11
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 10
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
206010011224 Cough Diseases 0.000 claims description 10
208000031361 Hiccup Diseases 0.000 claims description 10
206010029240 Neuritis Diseases 0.000 claims description 10
229910052727 yttrium Inorganic materials 0.000 claims description 10
208000014674 injury Diseases 0.000 claims description 9
125000003386 piperidinyl group Chemical group 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 8
229910052721 tungsten Inorganic materials 0.000 claims description 8
125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 7
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 7
125000002837 carbocyclic group Chemical group 0.000 claims description 7
238000001514 detection method Methods 0.000 claims description 7
IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 claims description 7
125000004193 piperazinyl group Chemical group 0.000 claims description 7
239000003491 tear gas Substances 0.000 claims description 7
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 6
210000004369 blood Anatomy 0.000 claims description 6
239000008280 blood Substances 0.000 claims description 6
210000001124 body fluid Anatomy 0.000 claims description 6
239000010839 body fluid Substances 0.000 claims description 6
230000001413 cellular effect Effects 0.000 claims description 6
210000002569 neuron Anatomy 0.000 claims description 6
208000033808 peripheral neuropathy Diseases 0.000 claims description 6
208000008589 Obesity Diseases 0.000 claims description 5
239000007789 gas Substances 0.000 claims description 5
230000002401 inhibitory effect Effects 0.000 claims description 5
230000007794 irritation Effects 0.000 claims description 5
125000000468 ketone group Chemical group 0.000 claims description 5
201000001119 neuropathy Diseases 0.000 claims description 5
235000020824 obesity Nutrition 0.000 claims description 5
239000007921 spray Substances 0.000 claims description 5
208000008035 Back Pain Diseases 0.000 claims description 4
235000002566 Capsicum Nutrition 0.000 claims description 4
206010019233 Headaches Diseases 0.000 claims description 4
239000006002 Pepper Substances 0.000 claims description 4
235000016761 Piper aduncum Nutrition 0.000 claims description 4
235000017804 Piper guineense Nutrition 0.000 claims description 4
235000008184 Piper nigrum Nutrition 0.000 claims description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
231100000869 headache Toxicity 0.000 claims description 4
230000000968 intestinal effect Effects 0.000 claims description 4
230000007823 neuropathy Effects 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
230000008733 trauma Effects 0.000 claims description 4
230000004580 weight loss Effects 0.000 claims description 4
125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 3
206010002383 Angina Pectoris Diseases 0.000 claims description 3
206010006482 Bronchospasm Diseases 0.000 claims description 3
206010068065 Burning mouth syndrome Diseases 0.000 claims description 3
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
208000013586 Complex regional pain syndrome type 1 Diseases 0.000 claims description 3
208000001640 Fibromyalgia Diseases 0.000 claims description 3
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
208000019695 Migraine disease Diseases 0.000 claims description 3
201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 claims description 3
239000000809 air pollutant Substances 0.000 claims description 3
231100001243 air pollutant Toxicity 0.000 claims description 3
230000007885 bronchoconstriction Effects 0.000 claims description 3
208000004967 femoral neuropathy Diseases 0.000 claims description 3
238000000099 in vitro assay Methods 0.000 claims description 3
208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
208000032184 meralgia paresthetica Diseases 0.000 claims description 3
230000001737 promoting effect Effects 0.000 claims description 3
208000004371 toothache Diseases 0.000 claims description 3
208000030507 AIDS Diseases 0.000 claims description 2
208000001387 Causalgia Diseases 0.000 claims description 2
208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 2
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 2
206010049567 Miller Fisher syndrome Diseases 0.000 claims description 2
206010028391 Musculoskeletal Pain Diseases 0.000 claims description 2
208000004983 Phantom Limb Diseases 0.000 claims description 2
206010056238 Phantom pain Diseases 0.000 claims description 2
206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
230000002146 bilateral effect Effects 0.000 claims description 2
208000014439 complex regional pain syndrome type 2 Diseases 0.000 claims description 2
201000006549 dyspepsia Diseases 0.000 claims description 2
208000014617 hemorrhoid Diseases 0.000 claims description 2
208000037805 labour Diseases 0.000 claims description 2
230000005906 menstruation Effects 0.000 claims description 2
206010027599 migraine Diseases 0.000 claims description 2
201000009985 neuronitis Diseases 0.000 claims description 2
201000008482 osteoarthritis Diseases 0.000 claims description 2
208000020431 spinal cord injury Diseases 0.000 claims description 2
238000001356 surgical procedure Methods 0.000 claims description 2
208000011580 syndromic disease Diseases 0.000 claims description 2
229930192474 thiophene Natural products 0.000 claims description 2
206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
239000002435 venom Substances 0.000 claims description 2
210000001048 venom Anatomy 0.000 claims description 2
231100000611 venom Toxicity 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 4
RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 2
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 2
IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 2
FHTHLMOKHXEATE-UHFFFAOYSA-N 1-[3,3-dimethyl-6-[[2-(2-methylpropoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]pyrido[2,3-d]pyrimidin-4-yl]amino]-2h-indol-1-yl]ethanone Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CN4C(C)=O)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F FHTHLMOKHXEATE-UHFFFAOYSA-N 0.000 claims 1
KTTBKTIZTKLPCG-UHFFFAOYSA-N 1-[3,3-dimethyl-6-[[2-(2-methylpropoxymethyl)-7-pyridin-2-ylpyrido[2,3-d]pyrimidin-4-yl]amino]-2h-indol-1-yl]ethanone Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CN4C(C)=O)(C)C)=CC=3)=C2C=CC=1C1=CC=CC=N1 KTTBKTIZTKLPCG-UHFFFAOYSA-N 0.000 claims 1
FZODJOGHTDQWND-UHFFFAOYSA-N 1-[6-[[2-(methoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]pyrido[2,3-d]pyrimidin-4-yl]amino]-3,3-dimethyl-2h-indol-1-yl]ethanone Chemical compound N=1C2=NC(COC)=NC(NC=3C=C4C(C(CN4C(C)=O)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F FZODJOGHTDQWND-UHFFFAOYSA-N 0.000 claims 1
DDHQDLDEVUBIAJ-UHFFFAOYSA-N 1-[6-[[7-(3-chloropyridin-2-yl)-2-(ethoxymethyl)pyrido[2,3-d]pyrimidin-4-yl]amino]-3,3-dimethyl-2h-indol-1-yl]ethanone Chemical compound N=1C2=NC(COCC)=NC(NC=3C=C4C(C(CN4C(C)=O)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1Cl DDHQDLDEVUBIAJ-UHFFFAOYSA-N 0.000 claims 1
VZTYUPSGOWLVBU-UHFFFAOYSA-N 2-(2-methylpropoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-n-(1,3,3-trimethyl-2h-indol-6-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CN4C)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F VZTYUPSGOWLVBU-UHFFFAOYSA-N 0.000 claims 1
XSVWHBRBBWRCSN-UHFFFAOYSA-N 2-(2-methylpropoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F XSVWHBRBBWRCSN-UHFFFAOYSA-N 0.000 claims 1
IOMOPRNICIERFL-UHFFFAOYSA-N 2-(2-methylpropoxymethyl)-7-pyridin-2-yl-n-(1,3,3-trimethyl-2h-indol-6-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CN4C)(C)C)=CC=3)=C2C=CC=1C1=CC=CC=N1 IOMOPRNICIERFL-UHFFFAOYSA-N 0.000 claims 1
QPACYHJNEDJKGO-UHFFFAOYSA-N 2-(2-methylpropoxymethyl)-7-pyridin-2-yl-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=CC=CC=N1 QPACYHJNEDJKGO-UHFFFAOYSA-N 0.000 claims 1
QWUYTCGIPVPPBA-UHFFFAOYSA-N 2-(ethoxymethyl)-7-(3-methylpyridin-2-yl)-n-(1,3,3-trimethyl-2h-indol-6-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC)=NC(NC=3C=C4C(C(CN4C)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C QWUYTCGIPVPPBA-UHFFFAOYSA-N 0.000 claims 1
ULYHLTQGPSTNIH-UHFFFAOYSA-N 2-(ethoxymethyl)-7-(3-methylpyridin-2-yl)-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC)=NC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C ULYHLTQGPSTNIH-UHFFFAOYSA-N 0.000 claims 1
DBHKMBAQFSWZDT-UHFFFAOYSA-N 2-(methoxymethyl)-7-(3-methylpyridin-2-yl)-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COC)=NC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C DBHKMBAQFSWZDT-UHFFFAOYSA-N 0.000 claims 1
GPWJOEUJUVTTEP-UHFFFAOYSA-N 2-(methoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)-1,8-naphthyridin-4-amine Chemical compound N=1C2=NC(COC)=CC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F GPWJOEUJUVTTEP-UHFFFAOYSA-N 0.000 claims 1
FOUNQNSFZOTUHB-UHFFFAOYSA-N 2-(methoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COC)=NC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F FOUNQNSFZOTUHB-UHFFFAOYSA-N 0.000 claims 1
FEWLQPOQAJRPHJ-UHFFFAOYSA-N 2-(phenylmethoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)quinazolin-4-amine Chemical compound C=1C=C2C(C)(C)CN(C)CC2=CC=1NC(C1=CC=C(C=C1N=1)C=2C(=CC=CN=2)C(F)(F)F)=NC=1COCC1=CC=CC=C1 FEWLQPOQAJRPHJ-UHFFFAOYSA-N 0.000 claims 1
PMUFZJDTZFHGMK-UHFFFAOYSA-N 2-methyl-n-[2-(2-methylpropoxymethyl)-7-(3-methylpyridin-2-yl)pyrido[2,3-d]pyrimidin-4-yl]-1,3-benzoxazol-6-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4OC(C)=NC4=CC=3)=C2C=CC=1C1=NC=CC=C1C PMUFZJDTZFHGMK-UHFFFAOYSA-N 0.000 claims 1
VFMAIJOSEDCWII-UHFFFAOYSA-N 2-methyl-n-[2-(2-methylpropoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]pyrido[2,3-d]pyrimidin-4-yl]-1,3-benzoxazol-6-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4OC(C)=NC4=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F VFMAIJOSEDCWII-UHFFFAOYSA-N 0.000 claims 1
BVHMUENOZZCADF-UHFFFAOYSA-N 4-methyl-n-[2-(2-methylpropoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]pyrido[2,3-d]pyrimidin-4-yl]-2,3-dihydro-1,4-benzoxazin-6-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4N(C)CCOC4=CC=3)=C2C=CC=1C1=NC=CC=C1C(F)(F)F BVHMUENOZZCADF-UHFFFAOYSA-N 0.000 claims 1
LBYNRSNRKHMYOF-UHFFFAOYSA-N 4-methyl-n-[2-(2-methylpropoxymethyl)-7-pyridin-2-ylpyrido[2,3-d]pyrimidin-4-yl]-2,3-dihydro-1,4-benzoxazin-6-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4N(C)CCOC4=CC=3)=C2C=CC=1C1=CC=CC=N1 LBYNRSNRKHMYOF-UHFFFAOYSA-N 0.000 claims 1
RPZSXJWMNHJINQ-UHFFFAOYSA-N 4-methyl-n-[2-(phenylmethoxymethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]quinazolin-4-yl]-2,3-dihydro-1,4-benzoxazin-6-amine Chemical compound C1=C2N(C)CCOC2=CC=C1NC(C1=CC=C(C=C1N=1)C=2C(=CC=CN=2)C(F)(F)F)=NC=1COCC1=CC=CC=C1 RPZSXJWMNHJINQ-UHFFFAOYSA-N 0.000 claims 1
VETKDCUTSMTNIN-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-(2-methylpropoxymethyl)-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1Cl VETKDCUTSMTNIN-UHFFFAOYSA-N 0.000 claims 1
BAGYILOEONTUTO-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-(ethoxymethyl)-n-(1,3,3-trimethyl-2h-indol-6-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC)=NC(NC=3C=C4C(C(CN4C)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1Cl BAGYILOEONTUTO-UHFFFAOYSA-N 0.000 claims 1
DRNCPHGTYCPFCG-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-(ethoxymethyl)-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC)=NC(NC=3C=C4C(C(CN(C)C4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1Cl DRNCPHGTYCPFCG-UHFFFAOYSA-N 0.000 claims 1
CAKUIYWZXNHBSY-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-2-[(2,6-dimethylmorpholin-4-yl)methyl]-n-(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)pyrido[3,2-d]pyrimidin-4-amine Chemical compound C1C(C)OC(C)CN1CC1=NC(NC=2C=C3C(C(CN(C)C3)(C)C)=CC=2)=C(N=CC(=C2)C=3C(=CC=CN=3)Cl)C2=N1 CAKUIYWZXNHBSY-UHFFFAOYSA-N 0.000 claims 1
OZDKRWMSINJUKE-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-n-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2-methylpropoxymethyl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4OCCOC4=CC=3)=C2C=CC=1C1=NC=CC=C1Cl OZDKRWMSINJUKE-UHFFFAOYSA-N 0.000 claims 1
NVHCVLVCJQEYRS-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-n-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(ethoxymethyl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC)=NC(NC=3C=C4OCCOC4=CC=3)=C2C=CC=1C1=NC=CC=C1Cl NVHCVLVCJQEYRS-UHFFFAOYSA-N 0.000 claims 1
NNGGKNWKQGWMGH-UHFFFAOYSA-N 7-(3-chloropyridin-2-yl)-n-(4,4-dimethyl-2,3-dihydro-1h-quinolin-7-yl)-2-(2-methylpropoxymethyl)pyrido[2,3-d]pyrimidin-4-amine Chemical compound N=1C2=NC(COCC(C)C)=NC(NC=3C=C4C(C(CCN4)(C)C)=CC=3)=C2C=CC=1C1=NC=CC=C1Cl NNGGKNWKQGWMGH-UHFFFAOYSA-N 0.000 claims 1
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