Claims for Patent: 10,160,747

Summary for Patent: 10,160,747

Title:	Compounds and methods for kinase modulation, and indications therefor
Abstract:	Disclosed are compounds of Formula I(b): ##STR00001## or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Ring A, Ring HD, J, each T, R.sup.3, R.sup.4, R.sup.5, each R.sup.7, and m are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.
Inventor(s):	Lin; Jack (Hercules, CA), Ibrahim; Prabha N. (Mountain View, CA), Albers; Aaron (San Francisco, CA), Buell; John (San Francisco, CA), Guo; Zuojun (Pasadena, CA), Pham; Phuongly (San Francisco, CA), Powers; Hannah (San Francisco, CA), Shi; Songyuan (Fremont, CA), Spevak; Wayne (Berkeley, CA), Wu; Guoxian (Foster City, CA), Zhang; Jiazhong (Foster City, CA), Zhang; Ying (Fremont, CA), Wu; Jeffrey (Berkeley, CA)
Assignee:	Plexxikon Inc. (Berkeley, CA)
Application Number:	15/460,095
Patent Claims:	1. A compound having Formula II(a) or II(b): ##STR00333## or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein: Ring A is phenyl, pyridyl, pyrimidinyl, or pyridazinyl; Y is N or CR.sup.9; R.sup.9 is hydrogen, halo, amino, alkyl optionally substituted with alkoxy or hydroxy, haloalkyl, or alkoxy; (i) is a single bond, wherein: Z.sup.1 is CH or N, Z.sup.2 is C(R.sup.12)(R.sup.12a) and Z.sup.3 is C(R.sup.13)(R.sup.13a); or Z.sup.1 is CH, Z.sup.2 is N(R.sup.12) and Z.sup.3 is C(R.sup.13)(R.sup.13a); or Z.sup.1 is CH, Z.sup.2 is C(R.sup.12)(R.sup.12a) and Z.sup.3 is N(R.sup.13); or (ii) is a double bond, wherein: Z.sup.1 is CH or N, Z.sup.2 is C(R.sup.12) and Z.sup.3 is C(R.sup.13); or Z.sup.1 is CH, Z.sup.2 is N and Z.sup.3 is C(R.sup.13); or Z.sup.1 is CH, Z.sup.2 is C(R.sup.12) and Z.sup.3 is N; R.sup.2 is ##STR00334## wherein: Ring B is a 5 or 6-membered saturated or unsaturated ring having 0-3 heteroatoms selected from O, N, and S; each Q is independently hydrogen, alkyl, halo, cyano, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, oxo, --R.sup.20OR.sup.21, --R.sup.20OR.sup.21, --R.sup.20OC(O)R.sup.21, --R.sup.20C(O)N(R.sup.24)(R.sup.25), --R.sup.20S(O).sub.tR.sup.22, --R.sup.20N(R.sup.24)(R.sup.25), or --R.sup.20N(R.sup.24)(R.sup.25), or --R.sup.20N(R.sup.24)C(O)R.sup.21, wherein each alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl or heterocycloalkylalkyl is independently optionally substituted with 1 to 3 groups each independently halo, oxo, amino, alkyl, haloalkyl or --R.sup.20OR.sup.21, Q.sup.1 is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, --R.sup.23OR.sup.21, --R.sup.23OR.sup.23OR.sup.21, --R.sup.23C(O)R.sup.21, --R.sup.23N(R.sup.24)(R.sup.25), --R.sup.23OC(O)R.sup.21, --R.sup.23C(O)OR.sup.21, --R.sup.23C(O)N(R.sup.24)(R.sup.25), or --R.sup.23S(O).sub.tR.sup.22 , wherein each alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl or heterocycloalkylalkyl is independently optionally substituted with 1 to 3 groups each independently halo, oxo, amino, alkyl, haloalkyl or --R.sup.20OR.sup.21; each Q.sup.3 is independently hydrogen, cyano, --S --C.sub.1-C.sub.2 alkyl, halo, C.sub.2-C.sub.3 alkenyl, C.sub.2-C.sub.3 alkynyl, C.sub.1-C.sub.3 alkoxy, cyclopropyl, amino, --N(H)(C.sub.1-C.sub.3alkyl), --N(H)C(O)C(H)=CH.sub.2 or C.sub.1-C.sub.3 alkyl, wherein each Q.sup.3 is optionally substituted with 1-3 substituents each independently halo, hydroxy or methoxy; Q.sup.4 is hydrogen, cyclopropyl, C.sub.1 -C.sub.4 alkoxy, or C.sub.1-C.sub.4 alkyl optionally substituted with 1-3 substituents each independently halo, hydroxy or methoxy; each R.sup.20 is independently alkylene, alkenylene, alkynylene or a direct bond; each R.sup.21 is independently hydrogen, alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl; each R.sup.22 is independently alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl; each R.sup.23 is independently alkylene, alkenylene or alkynylene; R.sup.24 and R.sup.25 are each independently hydrogen or alkyl; a is an integer from 0 to 3; each t is independently 0, 1 or 2; R.sup.3 is hydrogen or C.sub.1-C.sub.6 alkyl; each R.sup.6 is independently hydrogen, halo, C.sub.1-C.sub.3alkyl, or C.sub.1-C.sub.3 alkoxy; each R.sup.7 is independently C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.3-C.sub.6 cycloalkyl, 4-6 membered heterocycloalkyl, C.sub.3-C.sub.6cycloalkylalkyl, --S(O).sub.2alkyl, or a 4-6 membered heterocycloalkyl-C.sub.1-C.sub.6 alkyl, wherein each R.sup.7 is optionally substituted with 1 to 3 groups each independently hydroxy, halo, C.sub.1-C.sub.6 alkyl, cyano or C.sub.1-C.sub.6 haloalkyl; R.sup.9a is hydrogen, halo, hydroxy-C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkyl, or C.sub.1-C.sub.6 alkoxy-C.sub.1-C.sub.6 alkyl; each R.sup.11 is independently a 5-6 membered heterocycloalkyl, cyano, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6 haloalkyl, --C(O)OCH.sub.3, or --C(O)OH; R.sup.10 is C.sub.1-C.sub.6 alkyl, hydroxy-C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6 alkyl, 5-membered heteroaryl optionally substituted with alkyl, C.sub.3-C.sub.6 cycloalkyl, --C(O)OCH.sub.3, or --C(O)OH; R.sup.12 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, --(CH.sub.2).sub.0-2--N(R.sup.1b).sub.2, halo, C.sub.3-C.sub.6 cycloalkyl, --C(O)--C.sub.3-C.sub.6cycloalkyl, phenyl optionally substituted with 1-2 R.sup.11 groups, 5-6 membered heteroaryl optionally substituted with 1-2 R.sup.11 groups, or alkynyl optionally substituted with R.sup.10; R.sup.13 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, --C(O)--C.sub.1-C.sub.4 alkyl, halo, cyano, --(CH.sub.2).sub.0-2--N(R.sup.1b).sub.2, --C(O)NHCH.sub.3, amino, --NHC(O)CF.sub.3, C.sub.3-C.sub.6 cycloalkyl, --C(O)--C.sub.3-C.sub.6 cycloalkyl, phenyl optionally substituted with 1-2 R.sup.11 groups, 5-6 membered heteroaryl optionally substituted with 1-2 R.sup.11 groups, or alkynyl optionally substituted with R.sup.10; each R.sup.1b is independently hydrogen or alkyl; R.sup.12a is hydrogen; or R.sup.12 and R.sup.12a, together with the carbon to which they are attached, join to form a C.sub.3-6 spirocycloalkyl; or R.sup.12 and R.sup.12a form an oxo group; R.sup.13a is hydrogen; or R.sup.13 and R.sup.13a, together with the carbon to which they are attached, join to form a C.sub.3-6 spirocycloalkyl; or R.sup.13 and R.sup.13a form an oxo group; and m is 0, 1 or 2. 2. The compound of claim 1, wherein: R.sup.3 is hydrogen; each R.sup.6 is independently chloro, fluoro, methoxy, or methyl; each R.sup.7 is independently C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 alkoxy, hydroxy-C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.3alkoxy-C.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6 cycloalkyl, 4-6 membered heterocycloalkyl, C.sub.3-C.sub.6 cycloalkylalkyl, or a 4-6 membered heterocycloalkyl-C.sub.1-C.sub.6 alkyl; and m is 1 or 2. 3. The compound of claim 1 having Formula III(a): ##STR00335## or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein each R.sup.6a is independently hydrogen or fluoro. 4. The compound of claim 1 having Formula III(b) or III(c): ##STR00336## or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein each R.sup.6a is independently hydrogen or fluoro. 5. The compound of claim 1, wherein: Ring A is pyridyl or phenyl; and each R.sup.6 is hydrogen or one R.sup.6 is halo, alkyl or alkoxy. 6. The compound of claim 1, wherein: ##STR00337## is: ##STR00338## wherein: R.sup.7a is C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 alkyl optionally substituted with cyano, C.sub.1-C.sub.4 haloalkyl, cyclopropyl, halo, morpholinyl or cyano; and R.sup.7b is C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 alkyl optionally substituted with cyano, C.sub.1-C.sub.4 haloalkyl, halo or cyano. 7. The compound of claim 1, wherein: ##STR00339## wherein: R.sup.7a is cyclopropyl, --OCH.sub.3, --CH.sub.3, --CH.sub.2F, --CHF.sub.2, --CF.sub.3, --OCF.sub.3, --C(CH.sub.3).sub.3, --C(CN)(CH.sub.3).sub.2, F, Cl, Br, or cyano; and R.sup.7b is cyclopropyl, --OCH.sub.3, --CH.sub.3, --CH.sub.2F, --CHF.sub.2, --CF.sub.3, --C(CH.sub.3).sub.3, --C(CN)(CH.sub.3).sub.2, --OCF.sub.3, F, Cl, Br or cyano. 8. The compound of claim 1, wherein: ##STR00340## is: ##STR00341## 9. The compound of claim 1, wherein R.sup.2 is: ##STR00342## 10. The compound of claim 1, wherein R.sup.2 is: ##STR00343## wherein: each Q is independently hydrogen, --OCH.sub.3, hydroxy-C.sub.1-C.sub.4 alkyl, --CF.sub.3, --CHF.sub.2, --CH.sub.2F, --CH.sub.2CH.sub.3, or --CH.sub.3; Q.sup.1 is hydrogen, hydroxy-C.sub.1-C.sub.4 alkyl, --CF.sub.3, --CHF.sub.2, --CH.sub.2F, --CH.sub.2CH.sub.3, or --CH.sub.3; each Q.sup.3 is independently hydrogen, --OCH.sub.3, hydroxy-C.sub.1-C.sub.3 alkyl, --CF.sub.3, --CHF.sub.2, --CH.sub.2F, --CH.sub.2CH.sub.3, or --CH.sub.3; and Q.sup.4 is hydrogen, hydroxy-C.sub.1-C.sub.4 alkyl, --CF.sub.3, --CHF.sub.2, --CH.sub.2F,--CH.sub.2CH.sub.3, or --CH.sub.3. 11. The compound of claim 1, wherein R.sup.2 is: ##STR00344## 12. The compound of claim 1, wherein: R.sup.12 is hydrogen; --CH.sub.3; Cl; F; Br; cyclopropyl; phenyl; pyridyl optionally substituted with morpholinyl, ethoxy, methoxy, cyano, --CF.sub.3, --CHF.sub.2, --CH.sub.2F or --CH.sub.3; ethynyl optionally substituted with --C(CH.sub.3).sub.3, --C(CH.sub.3).sub.2OH, cyclopropyl, --C(O)OCH.sub.3, --C(O)OH, or methoxymethyl; or imidazolyl optionally substituted with methyl, --C(O)OCH.sub.3, or --C(O)OH; and R.sup.13 is hydrogen, --C(O)CH.sub.3, --C(O)CH.sub.2CH.sub.3, F, Cl, Br, cyano, cyclopropyl, --C(O)-cyclopropyl, --C(O)NHCH.sub.3, --OCH.sub.3, --OCH.sub.2CH.sub.3, --CH.sub.2CH.sub.3, amino, or --NHC(O)CF.sub.3. 13. The compound of claim 1, wherein: R.sup.12 is phenyl; pyridyl optionally substituted with morpholinyl, ethoxy, methoxy, cyano, --CF.sub.3, --CHF.sub.2, --CH.sub.2F, or --CH.sub.3; or ethynyl optionally substituted with --C(CH.sub.3).sub.3, --C(CH.sub.3).sub.2OH, cyclopropyl, --C(O)OCH.sub.3, --C(O)OH, or methoxymethyl; and R.sup.13 is hydrogen, --C(O)CH.sub.3, --C(O)CH.sub.2CH.sub.3, F, Cl, Br, cyano, cyclopropyl, --C(O)-cyclopropyl, --C(O)NHCH.sub.3, --OCH.sub.3, --OCH.sub.2CH.sub.3, --CH.sub.2CH.sub.3, amino, or --NHCOCF.sub.3. 14. The compound of claim 4 having Formula III(b): ##STR00345## or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein: R.sup.12 is phenyl; pyridyl optionally substituted with morpholinyl, ethoxy, methoxy, cyano, --CF.sub.3, --CHF.sub.2, --CH.sub.2F, or --CH.sub.3; or ethynyl optionally substituted with --C(CH.sub.3).sub.3, --C(CH.sub.3).sub.2OH, cyclopropyl, --C(O)OCH.sub.3, --C(O)OH or methoxymethyl; and R.sup.13 is hydrogen. 15. The compound of claim 4 having Formula III(c): ##STR00346## or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R.sup.13 is --C(O)CH.sub.3, --C(O)CH.sub.2CH.sub.3, F, Cl, Br, cyano, cyclopropyl, --C(O)-cyclopropyl, --C(O)NHCH.sub.3, --OCH.sub.3, --OCH.sub.2CH.sub.3, --CH.sub.2CH.sub.3, amino, or --NHC(O)CF.sub.3. 16. A compound selected from: TABLE-US-00011 No. Compound Structure P-0001 ##STR00347## P-0002 ##STR00348## P-0003 ##STR00349## P-0004 ##STR00350## P-0005 ##STR00351## P-0006 ##STR00352## P-0007 ##STR00353## P-0008 ##STR00354## P-0009 ##STR00355## P-0010 ##STR00356## P-0011 ##STR00357## P-0012 ##STR00358## P-0013 ##STR00359## P-0014 ##STR00360## P-0015 ##STR00361## P-0016 ##STR00362## P-0017 ##STR00363## P-0018 ##STR00364## P-0019 ##STR00365## P-0020 ##STR00366## P-0021 ##STR00367## P-0022 ##STR00368## P-0023 ##STR00369## P-0024 ##STR00370## P-0025 ##STR00371## P-0026 ##STR00372## P-0027 ##STR00373## P-0028 ##STR00374## P-0029 ##STR00375## P-0030 ##STR00376## P-0031 ##STR00377## P-0032 ##STR00378## P-0033 ##STR00379## P-0034 ##STR00380## P-0035 ##STR00381## P-0036 ##STR00382## P-0037 ##STR00383## P-0038 ##STR00384## P-0039 ##STR00385## P-0040 ##STR00386## P-0041 ##STR00387## P-0042 ##STR00388## P-0043 ##STR00389## P-0044 ##STR00390## P-0045 ##STR00391## P-0046 ##STR00392## P-0047 ##STR00393## P-0048 ##STR00394## P-0049 ##STR00395## P-0050 ##STR00396## P-0051 ##STR00397## P-0052 ##STR00398## P-0053 ##STR00399## P-0054 ##STR00400## P-0055 ##STR00401## P-0056 ##STR00402## P-0057 ##STR00403## P-0058 ##STR00404## P-0059 ##STR00405## P-0060 ##STR00406## P-0061 ##STR00407## P-0062 ##STR00408## P-0063 ##STR00409## P-0064 ##STR00410## P-0065 ##STR00411## P-0066 ##STR00412## P-0067 ##STR00413## P-0068 ##STR00414## P-0069 ##STR00415## P-0070 ##STR00416## P-0071 ##STR00417## P-0072 ##STR00418## P-0073 ##STR00419## P-0074 ##STR00420## P-0075 ##STR00421## P-0076 ##STR00422## P-0077 ##STR00423## P-0078 ##STR00424## P-0079 ##STR00425## P-0080 ##STR00426## P-0081 ##STR00427## P-0082 ##STR00428## P-0083 ##STR00429## P-0084 ##STR00430## P-0085 ##STR00431## P-0086 ##STR00432## P-0087 ##STR00433## P-0088 ##STR00434## P-0089 ##STR00435## P-0090 ##STR00436## P-0091 ##STR00437## P-0092 ##STR00438## P-0093 ##STR00439## P-0094 ##STR00440## P-0095 ##STR00441## P-0096 ##STR00442## P-0097 ##STR00443## P-0098 ##STR00444## P-0099 ##STR00445## P-0100 ##STR00446## P-0101 ##STR00447## P-0102 ##STR00448## P-0103 ##STR00449## P-0104 ##STR00450## P-0105 ##STR00451## P-0106 ##STR00452## P-0107 ##STR00453## P-0108 ##STR00454## P-0109 ##STR00455## P-0110 ##STR00456## P-0111 ##STR00457## P-0112 ##STR00458## P-0113 ##STR00459## P-0116 ##STR00460## P-0117 ##STR00461## P-0118 ##STR00462## P-0119 ##STR00463## P-0120 ##STR00464## P-0121 ##STR00465## P-0122 ##STR00466## P-0130 ##STR00467## P-0131 ##STR00468## P-0133 ##STR00469## P-0134 ##STR00470## P-0135 ##STR00471## P-0136 ##STR00472## P-0137 ##STR00473## P-0270 ##STR00474## P-0272 ##STR00475## P-0274 ##STR00476## P-0138 ##STR00477## P-0139 ##STR00478## P-0140 ##STR00479## P-0141 ##STR00480## P-0142 ##STR00481## P-0143 ##STR00482## P-0144 ##STR00483## P-0145 ##STR00484## P-0146 ##STR00485## P-0147 ##STR00486## P-0148 ##STR00487## P-0149 ##STR00488## P-0150 ##STR00489## P-0151 ##STR00490## P-0152 ##STR00491## P-0153 ##STR00492## P-0154 ##STR00493## P-0155 ##STR00494## P-0156 ##STR00495## P-0157 ##STR00496## P-0158 ##STR00497## P-0163 ##STR00498## P-0164 ##STR00499## P-0165 ##STR00500## P-0166 ##STR00501## P-0167 ##STR00502## P-0168 ##STR00503## P-0169 ##STR00504## P-0170 ##STR00505## P-0171 ##STR00506## P-0172 ##STR00507## P-0173 ##STR00508## P-0174 ##STR00509## P-0175 ##STR00510## P-0176 ##STR00511## P-0177 ##STR00512## P-0178 ##STR00513## P-0179 ##STR00514## P-0180 ##STR00515## P-0181 ##STR00516## P-0182 ##STR00517## P-0183 ##STR00518## P-0184 ##STR00519## P-0185 ##STR00520## P-0186 ##STR00521## P-0187 ##STR00522## P-0188 ##STR00523## P-0189 ##STR00524## P-0190 ##STR00525## P-0191 ##STR00526## P-0192 ##STR00527## P-0193 ##STR00528## P-0194 ##STR00529## P-0195 ##STR00530## P-0196 ##STR00531## P-0197 ##STR00532## P-0198 ##STR00533## P-0199 ##STR00534## P-0200 ##STR00535## P-0201 ##STR00536## P-0202 ##STR00537## P-0203 ##STR00538## P-0204 ##STR00539## P-0205 ##STR00540## P-0206 ##STR00541## P-0207 ##STR00542## P-0208 ##STR00543## P-0209 ##STR00544## P-0210 ##STR00545## P-0211 ##STR00546## P-0212 ##STR00547## P-0213 ##STR00548## P-0214 ##STR00549## P-0215 ##STR00550## P-0216 ##STR00551## P-0217 ##STR00552## P-0218 ##STR00553## P-0219 ##STR00554## P-0220 ##STR00555## P-0221 ##STR00556## P-0222 ##STR00557## P-0223 ##STR00558## P-0224 ##STR00559## P-0225 ##STR00560## P-0226 ##STR00561## P-0227 ##STR00562## P-0228 ##STR00563## P-0229 ##STR00564## P-0230 ##STR00565## P-0231 ##STR00566## P-0232 ##STR00567## P-0233 ##STR00568## P-0234 ##STR00569## P-0235 ##STR00570## P-0236 ##STR00571## P-0237 ##STR00572## P-0238 ##STR00573## P-0239 ##STR00574## P-0240 ##STR00575## P-0241 ##STR00576## P-0242 ##STR00577## P-0243 ##STR00578## P-0244 ##STR00579## P-0245 ##STR00580## P-0246 ##STR00581## P-0247 ##STR00582## P-0248 ##STR00583## P-0249 ##STR00584## P-0250 ##STR00585## P-0251 ##STR00586## P-0252 ##STR00587## P-0253 ##STR00588## P-0254 ##STR00589## P-0255 ##STR00590## P-0256 ##STR00591## P-0257 ##STR00592## P-0258 ##STR00593## P-0259 ##STR00594## P-0260 ##STR00595## P-0261 ##STR00596## P-0262 ##STR00597## P-0263 ##STR00598## P-0264 ##STR00599## P-0265 ##STR00600## P-0266 ##STR00601## P-0267 ##STR00602## P-0268 ##STR00603## P-0269 ##STR00604## P-0271 ##STR00605## P-0273 ##STR00606## or a pharmaceutically acceptable salt thereof. 17. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt, deuterated analog, a tautomer or a stereoisomer thereof, and a pharmaceutically acceptable carrier. 18. The pharmaceutical composition of claim 17 further comprising a second pharmaceutical agent selected from the group consisting of an anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory agent and an immunosuppressive agent. 19. The pharmaceutical composition according to claim 18, wherein the second pharmaceutical agent is i) an alkylating agent selected from adozelesin, altretamine, bizelesin, busulfan, carboplatin, carboquone, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, estramustine, fotemustine, hepsulfam, ifosfamide, improsulfan, irofulven, lomustine, mechlorethamine, melphalan, oxaliplatin, piposulfan, semustine, streptozocin, temozolomide, thiotepa, and treosulfan; ii) an antibiotic selected from bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, menogaril, mitomycin, mitoxantrone, neocarzinostatin, pentostatin, and plicamycin; iii) an antimetabolite selected from the group consisting of azacitidine, capecitabine, cladribine, clofarabine, cytarabine, decitabine, floxuridine, fludarabine, 5-fluorouracil, ftorafur, gemcitabine, hydroxyurea, mercaptopurine, methotrexate, nelarabine, pemetrexed, raltitrexed, thioguanine, and trimetrexate; iv) an antibody therapy agent selected from alemtuzumab, bevacizumab, cetuximab, galiximab, gemtuzumab, nivolumab, panitumumab, pembrolizumab, pertuzumab, rituximab, tositumomab, trastuzumab, and 90 Y ibritumomab tiuxetan; v) a hormone or hormone antagonist selected from the group consisting of anastrozole, androgens, buserelin, diethylstilbestrol, exemestane, flutamide, fulvestrant, goserelin, idoxifene, letrozole, leuprolide, magestrol, raloxifene, tamoxifen, and toremifene; vi) a taxane selected from DJ-927, docetaxel, TPI 287, paclitaxel and DHA-paclitaxel; vii) a retinoid selected from alitretinoin, bexarotene, fenretinide, isotretinoin, and tretinoin; viii) an alkaloid selected from etoposide, homoharringtonine, teniposide, vinblastine, vincristine, vindesine, and vinorelbine; ix) an antiangiogenic agent selected from AE-941 (GW786034, Neovastat), ABT-510, 2-methoxyestradiol, lenalidomide, and thalidomide; x) a topoisomerase inhibitor selected from amsacrine, edotecarin, exatecan, irinotecan, SN-38 (7-ethyl-10-hydroxy-camptothecin), rubitecan, topotecan, and 9-aminocamptothecin; xi) a kinase inhibitor selected from erlotinib, gefitinib, flavopiridol, imatinib mesylate, lapatinib, sorafenib, sunitinib malate, AEE-788, AG-013736, AMG 706, AMN107, BMS-354825, BMS-599626, UCN-01 (7-hydroxystaurosporine), vemurafenib, dabrafenib, trametinib, cobimetinib selumetinib and vatalanib; xii) a targeted signal transduction inhibitor selected from bortezomib, geldanamycin, and rapamycin; xiii) a biological response modifier selected from imiquimod, interferon-.alpha.and interleukin-2; xiv) an IDO inhibitor; xv) a chemotherapeutic agent selected from 3-AP (3-amino-2-carboxyaldehyde thiosemicarbazone), altrasentan, aminoglutethimide, anagrelide, asparaginase, bryostatin-1, cilengitide, elesclomol, eribulin mesylate (E7389), ixabepilone, lonidamine, masoprocol, mitoguanazone, oblimersen, sulindac, testolactone, tiazofurin, a mTOR inhibitor, a PI3K inhibitor, a Cdk4 inhibitor, an Akt inhibitor, a Hsp90 inhibitor, a farnesyltransferase inhibitor or an aromatase inhibitor (anastrozole letrozole exemestane); xvi) a Mek inhibitor; xvii) a tyrosine kinase inhibitor; or xviii) an EGFR inhibitor. 20. A method for treatment of a disease or condition modulated by FLT3, CSF1R, or c-kit, wherein the disease is an inflammatory disease, an inflammatory condition, an autoimmune disease or cancer, said method comprising administering to a subject suffering from the disease a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, deuterated analog, a tautomer or a stereoisomer thereof. 21. A method for treating a subject with a disease or condition mediated by FLT3, CSF1R or c-kit, said method comprising administering to the subject an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, deuterated analog, a tautomer or a stereoisomer thereof, wherein the disease or condition is acute myeloid leukemia, stem cell ablation and myelopreparation for stem cell transplant, primary progressive multiple sclerosis, Erdheim-Chester Disease, Langerhans cell histocytosis, hairy cell leukemia, HIV, glioblastoma, anterior or posterior eye disease, lysosomal storage diseases, complex regional pain syndrome, neuro-inflammation, neuroinflammatory disorders, binswager type dementia, dementia with lewy bodie, cerebral palsy, progressive supranuclear palsy, vascular dementias, multi infarct dementia, fronto temporal dementia, pseudo-dementia, bladder cancer, basal cell carcinoma, cholangiocarcinoma, colon cancer, endometrial cancer, esophageal cancer, Ewing's sarcoma, gastric cancer, glioma, hepatocellular carcinoma, Hodgkin lymphoma, laryngeal carcinoma, leukemia, liver cancer, lung cancer, melanoma, mesothelioma, pancreatic cancer, rectal cancer, renal cancer, squamous cell carcinoma, T cell lymphoma, thyroid cancer, monocytic leukemia, pheochromocytoma, malignant peripheral nerve cell tumors, malignant peripheral nerve sheath tumors (MPNST), cutaneous and plexiform neurofibromas, leiomyoadenomatoid tumor, fibroids, uterine fibroids, leiomyosarcoma, papillary thyroid cancer, anaplastic thyroid cancer, medullary thyroid cancer, follicular thyroid cancer, hurthle cell carcinoma, thyroid cancer, ascites, malignant ascites, mesothelioma, salivary gland tumors, mucoepidermoid carcinoma of the salivary gland, acinic cell carcinoma of the salivary gland, gastrointestinal stromal tumors (GIST), tumors that cause effusions in potential spaces of the body, pleural effusions, pericardial effusions, peritoneal effusions aka ascites, giant cell tumors (GCT), GCT of bone other sarcomas, tumor angiogenesis, paracrine tumor growth or tumors that express aberrantly or otherwise a FLT3 ligand, or activating mutations or translocations of any of the foregoing. 22. A method for treating a subject with a disease or condition mediated by a FLT3, CSF1R or c-kit, said method comprising administering to the subject an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, deuterated analog, a tautomer or a stereoisomer thereof, wherein the disease or condition is lysosomal storage selected from the group consisting of mucolipodosis, alpha-mannosidosis; aspartylglucosaminuria; Batten disease; beta-mannosidosis; cystinosis; Danon disease; Fabry disease; Farber disease; fucosidosis; galactosialidosis; Gaucher disease; gangliosidosis; Krabbe disease; metachromatic leukodystrophy; mucopolysaccharidoses disorders; aspartylglucosaminuria; Batten disease; beta-mannosidosis; cystinosis; Danon disease; Fabry disease; Farber disease; fucosidosis; galactosialidosis; Gaucher disease; gangliosidosis; Krabbe disease; metachromatic leukodystrophy; mucopolysaccharidoses disorders; mucolipidosis type I (Sialidosis); Mucolipidosis type II (I-Cell disease); Mucolipidosis type III (Pseudo-Hurler polydystrophy); Mucolipidosis type IV; multiple sulfatase deficiency; Niemann-Pick types A, B, C; Pompe disease (glycogen storage disease); pycnodysostosis; Sandhoff disease; Schindler disease; Salla disease/sialic acid storage disease; Tay-Sachs; and Wolman disease. 23. The method of claim 20, wherein FLT3 kinase is a mutated form comprising a FLT3 internal tandem duplication (ITD) mutation. 24. The method of claim 23, wherein mutated FLT3 kinase further comprises a D835 mutation, a F691L mutation, or both D835 and F691L mutations. 25. The method according to claim 24, wherein mutated FLT3 kinase further comprises a D835Y mutation, a F691L mutation, or both D835Y and F691L mutations.

Details for Patent 10,160,747

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2036-03-16
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2036-03-16
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2036-03-16