Claims for Patent: 10,047,096

Summary for Patent: 10,047,096

Title:	Substituted pyridobenzodiazepinone-derivatives and use thereof
Abstract:	The present application relates to novel (3-hydroxyphenyl)amino-substituted pyrido[2,3-b][1,5]benzodiazepin-5-one derivatives, to processes for preparation thereof, to the use thereof alone or in combination for treatment and/or prevention of diseases and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially of angiogenic disorders and hyperproliferative disorders in which neovascularization plays a role, for example ophthalmological disorders and cancers and tumours. Such treatments can be effected as monotherapy or else in combination with other medicaments or further therapeutic measures.
Inventor(s):	Schall; Andreas (Wuppertal, DE), Klar; Jurgen (Wuppertal, DE), Lobell; Mario (Wuppertal, DE), Schirok; Hartmut (Langenfeld, DE), Telser; Joachim (Wuppertal, DE), Muller; Steffen (Essen, DE), Brohm; Dirk (Mettmann, DE), Briem; Hans (Berlin, DE), Jori en; Hannah (Heiligenhaus, DE), Keldenich; Joerg (Berlin, DE), Bottger; Michael (Wuppertal, DE), Von Degenfeld; Georges (Leverkusen, DE), Schlange; Thomas (Haan, DE), Bomer; Ulf (Glienicke, DE), Lindner; Niels (Wuppertal, DE), Eilken; Hanna (Wuppertal, DE), Hristodorov; Dmitrij (Wuppertal, DE), Wasnaire; Pierre (Dusseldorf, DE), Gericke; Kersten Matthias (Wuppertal, DE), Barfacker; Lars (Dusseldorf, DE)
Assignee:	Bayer Pharma Aktiengesellschaft (Berlin, DE)
Application Number:	15/529,043
Patent Claims:	1. A compound of formula (I) ##STR00322## wherein: R.sup.1 is hydrogen, halogen, hydroxyl, (C.sub.1-C.sub.4)-alkyl, --NH--C(.dbd.O)--R.sup.4, --NH--C(.dbd.O)--O--R.sup.5 or --NH--SO.sub.2--R.sup.6, wherein R.sup.4 is hydrogen or (C.sub.1-C.sub.4)-alkyl; R.sup.5 is (C.sub.1-C.sub.4)-alkyl; and R.sup.6 is (C.sub.1-C.sub.4)-alkyl or phenyl; R.sup.2 is hydrogen, fluorine, chlorine, methyl or methoxy; R.sup.3 is hydrogen, fluorine, chlorine or methyl; and G is cyano, hydroxycarbonyl, --C(.dbd.O)--NR.sup.7AR.sup.7B or --CH.sub.2--NR.sup.8AR.sup.8B, wherein R.sup.7A is hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by hydroxyl, (C.sub.1-C.sub.4)-alkoxy or up to trisubstituted by fluorine; R.sup.7B is hydrogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.6)-cycloalkyl, phenyl, 4- to 7-membered heterocyclyl or 5- to 10-membered heteroaryl; wherein (C.sub.1-C.sub.6)-alkyl is optionally up to hexasubstituted by fluorine and up to disubstituted, identically or differently, by a radical selected from the group consisting of --OR.sup.9, --O--(CH.sub.2CH.sub.2O).sub.n--R.sup.10, --SR.sup.11, --NR.sup.12AR.sup.12B, --C(.dbd.O)--NR.sup.13AR.sup.13B, (C.sub.3-C.sub.6)-cycloalkyl, (C.sub.4-C.sub.6)-cycloalkenyl, phenyl, 4- to 7-membered heterocyclyl and 5- or 6-membered heteroaryl; and wherein (i) the cycloalkyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.4)-alkyl, hydroxyl, (C.sub.1-C.sub.4)-alkoxy, hydroxycarbonyl and (C.sub.1-C.sub.4)-alkoxy carbonyl; (ii) the phenyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, (C.sub.1-C.sub.4)-alkyl and (C.sub.1-C.sub.4)-alkoxy; (iii) the heterocyclyl groups are optionally up to trisubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.4)-alkyl, hydroxyl, oxo, hydroxycarbonyl and (C.sub.1-C.sub.4)-alkoxycarbonyl; and (iv) the heteroaryl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, (C.sub.1-C.sub.4)-alkyl and (C.sub.1-C.sub.4)-alkoxy; and wherein R.sup.9 is hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by 4- to 6-membered heterocyclyl; R.sup.10 is hydrogen or (C.sub.1-C.sub.4)-alkyl; R.sup.11 is (C.sub.1-C.sub.4)-alkyl; R.sup.12A, R.sup.12B, R.sup.13A and R.sup.13B are independently hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by hydroxyl; and n is an integer from 1 to 10; or R.sup.7A and R.sup.7B are joined to one another and, together with the nitrogen atom to which they are bonded, form a 4- to 10-membered heterocycle which optionally contains up to 2 further ring heteroatoms selected from the group consisting of N, O and S, and which is optionally up to tetrasubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.4)-alkyl, oxo, --OR.sup.14, --NR.sup.15AR.sup.15B, --C(.dbd.O)--NR.sup.16AR.sup.16B and phenyl; wherein (C.sub.1-C.sub.4)-alkyl is optionally substituted by hydroxy or up to three times by fluorine; and wherein R.sup.14 is hydrogen, (C.sub.1-C.sub.4)-alkyl or phenyl; wherein (C.sub.1-C.sub.4)-alkyl is optionally substituted by hydroxyl, --C(.dbd.O)--NR.sup.17AR.sup.17B, (C.sub.3-C.sub.6)-cycloalkyl or up to trisubstituted by fluorine; and R.sup.15A, R.sup.15B, R.sup.16A, R.sup.16B, R.sup.17A and R.sup.17B are independently hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by hydroxyl; R.sup.8A is hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by hydroxyl, (C.sub.1-C.sub.4)-alkoxy or up to trisubstituted by fluorine; and R.sup.8B is hydrogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.6)-cycloalkyl, phenyl, 4- to 7-membered heterocyclyl or 5- to 10-membered heteroaryl; wherein (C.sub.1-C.sub.6)-alkyl is optionally up to hexasubstituted by fluorine and up to disubstituted, identically or differently, by a radical selected from the group consisting of --OR.sup.18, --O--(CH.sub.2CH.sub.2O).sub.p--R.sup.19, --SR.sup.20, --NR.sup.21AR.sup.21B, --C(.dbd.O)--NR.sup.22AR.sup.22B, (C.sub.3-C.sub.6)-cycloalkyl, (C.sub.4-C.sub.6)-cycloalkenyl, phenyl, 4- to 7-membered heterocyclyl and 5- or 6-membered heteroaryl; and wherein (i) the cycloalkyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.4)-alkyl, hydroxyl, (C.sub.1-C.sub.4)-alkoxy, hydroxycarbonyl and (C.sub.1-C.sub.4)-alkoxycarbonyl; (ii) the phenyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, (C.sub.1-C.sub.4)-alkyl and (C.sub.1-C.sub.4)-alkoxy; (iii) the heterocyclyl groups are optionally up to trisubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.4)-alkyl, hydroxyl, oxo, hydroxycarbonyl and (C.sub.1-C.sub.4)-alkoxycarbonyl; and (iv) the heteroaryl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, (C.sub.1-C.sub.4)-alkyl and (C.sub.1-C.sub.4)-alkoxy; and wherein R.sup.18 is hydrogen or (C.sub.1-C.sub.4)-alky optionally substituted by 4- to 6-membered heterocyclyl; R.sup.19 is hydrogen or (C.sub.1-C.sub.4)-alkyl; R.sup.20 is (C.sub.1-C.sub.4)-alkyl; R.sup.21A, R.sup.21B, R.sup.22A and R.sup.22B are independently hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by hydroxyl; and p is an integer from 1 to 10; or R.sup.8A and R.sup.8B are joined to one another and, together with the nitrogen atom to which they are bonded, form a 4- to 10-membered heterocycle which optionally contains up to 2 further ring heteroatoms selected from the group consisting of N, O and S, and which is optionally up to tetrasubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.4)-alkyl, oxo, --OR.sup.23, --NR.sup.24AR.sup.24B, --C(.dbd.O)--NR.sup.25AR.sup.25B and phenyl; wherein (C.sub.1-C.sub.4)-alkyl is optionally substituted by hydroxy or up to three times by fluorine; and wherein R.sup.23 is hydrogen, (C.sub.1-C.sub.4)-alkyl or phenyl; wherein (C.sub.1-C.sub.4)-alkyl is optionally substituted by hydroxyl, --C(.dbd.O)--NR.sup.26AR.sup.26B, (C.sub.3-C.sub.6)-cycloalkyl or up to trisubstituted by fluorine; and R.sup.24A, R.sup.24B, R.sup.25A, R.sup.25B, R.sup.26A and R.sup.26B are independently hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by hydroxyl, or a salt, a solvate or a solvate of a salt thereof. 2. The compound of formula (I) according to claim 1, wherein: R.sup.1 is hydrogen, fluorine, chlorine, (C.sub.1-C.sub.4)-alkyl or --NH--SO.sub.2--R.sup.6, wherein R.sup.6 is (C.sub.1-C.sub.4)-alkyl or phenyl; R.sup.2 is hydrogen, fluorine, chlorine or methyl; R.sup.3 is hydrogen, fluorine, chlorine or methyl; and G is cyano, --C(.dbd.O)--NR.sup.7AR.sup.7B or --CH.sub.2--NR.sup.8AR.sup.8B, wherein R.sup.7A is hydrogen, methyl, ethyl, 2-hydroxyethyl, 2-methoxyethyl or 2-ethoxyethyl; wherein methyl and ethyl are optionally up to trisubstituted by fluorine; R.sup.7B is hydrogen, (C.sub.1-C.sub.4)-alkyl or (C.sub.3-C.sub.6)-cycloalkyl; wherein (C.sub.1-C.sub.4)-alkyl is optionally up to trisubstituted by fluorine and up to disubstituted, identically or differently, by a radical selected from the group consisting of --OR.sup.9, --SR.sup.11, --NR.sup.12AR.sup.12B, (C.sub.3-C.sub.6)-cycloalkyl and phenyl; and wherein (i) the cycloalkyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, methyl, ethyl, hydroxyl, methoxy, ethoxy, hydroxycarbonyl, methoxycarbonyl and ethoxycarbonyl; and (ii) the phenyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, methyl, ethyl, methoxy and ethoxy; and wherein R.sup.9 is hydrogen, methyl or ethyl; R.sup.11 is methyl or ethyl; and R.sup.12A and R.sup.12B are independently hydrogen, methyl, ethyl or 2-hydroxyethyl; or R.sup.7A and R.sup.7B are joined to one another and, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered heterocycle which optionally contains one further ring heteroatom selected from the group consisting of N, O and S, and which is optionally up to tetrasubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.3)-alkyl, oxo, --OR.sup.14, NR.sup.15AR.sup.15B, --C(.dbd.O)--NR.sup.16AR.sup.16B and phenyl; wherein (C.sub.1-C.sub.3)-alkyl is optionally substituted by hydroxy or up to three times by fluorine; and wherein R.sup.14 is hydrogen, methyl or ethyl; and R.sup.15A, R.sup.15B, R.sup.16A and R.sup.16B are independently hydrogen, methyl or ethyl; R.sup.8A is hydrogen or (C.sub.1-C.sub.4)-alkyl optionally substituted by hydroxyl, methoxy, ethoxy or up to trisubstituted by fluorine; and R.sup.8B is hydrogen, (C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.6)-cycloalkyl, phenyl, 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl; wherein (C.sub.1-C.sub.6)-alkyl is optionally up to trisubstituted by fluorine and up to disubstituted, identically or differently, by a radical selected from the group consisting of --OR.sup.18, --SR.sup.20, --NR.sup.21AR.sup.21B, --C(.dbd.O)--NR.sup.22AR.sup.22B, (C3-C6)-cycloalkyl, phenyl, 5- or 6-membered heterocyclyl and 5- or 6-membered heteroaryl; and wherein (i) the cycloalkyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.3)-alkyl, hydroxyl, (C.sub.1-C.sub.3)-alkoxy, hydroxycarbonyl, methoxycarbonyl and ethoxycarbonyl; (ii) the phenyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, methyl, ethyl, methoxy and ethoxy; (iii) the heterocyclyl groups are optionally up to trisubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.3)-alkyl, hydroxyl, oxo, hydroxycarbonyl, methoxycarbonyl and ethoxycarbonyl; and (iv) the heteroaryl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, (C.sub.1-C.sub.3)-alkyl and (C.sub.1-C.sub.3)-alkoxy; and wherein R.sup.18 is hydrogen or (C.sub.1-C.sub.3)-alkyl; R.sup.20 is (C.sub.1-C.sub.3)-alkyl; and R.sup.21A, R.sup.21B, R.sup.22A and R.sup.22B are independently hydrogen or (C.sub.1-C.sub.3)-alkyl optionally substituted by hydroxyl; or R.sup.8A and R.sup.8B are joined to one another and, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered heterocycle which optionally contains one further ring heteroatom from the group of N, O and S, and which is optionally up to tetrasubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.4)-alkyl, oxo, --OR.sup.23, --NR24AR.sup.24B, --C(.dbd.O)--NR.sup.25AR.sup.25B and phenyl; wherein (C.sub.1-C.sub.4)-alkyl is optionally substituted by hydroxy or up to three times by fluorine; and wherein R.sup.23 is hydrogen or (C.sub.1-C.sub.3)-alkyl; wherein (C.sub.1-C.sub.3)-alkyl is optionally substituted by hydroxyl, (C.sub.3-C.sub.6)-cycloalkyl or up to trisubstituted by fluorine; and R.sup.24A, R.sup.24B, R.sup.25A and R.sup.25B are independently hydrogen or (C.sub.1-C.sub.3)-alkyl optionally substituted by hydroxyl, or a salt, a solvate or a solvate of a salt thereof. 3. The compound of formula (I) according to claim 1, wherein: R.sup.1 is hydrogen, fluorine, chlorine or (C.sub.1-C.sub.4)-alkyl; R.sup.2 is hydrogen or fluorine; R.sup.3 is hydrogen, fluorine, chlorine or methyl; and G is --C(.dbd.O)--NR.sup.7AR.sup.7B or --CH.sub.2--NR.sup.8AR.sup.8B, wherein R.sup.7A is hydrogen, methyl or ethyl; R.sup.7B is methyl, ethyl, 2-hydroxyethyl or cyclohexyl; wherein cyclohexyl is optionally up to disubstituted by hydroxyl; or R.sup.7A and R.sup.7B are joined to one another and, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered heterocycle which optionally contains one further ring heteroatom selected from the group consisting of N and O, and which is optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of methyl, ethyl, oxo and hydroxyl; wherein the methyl and ethyl are optionally substituted by hydroxyl; R.sup.8A is hydrogen or (C.sub.1-C.sub.4)-alkyl; and R.sup.8B is (C.sub.1-C.sub.6)-alkyl, (C.sub.3-C.sub.6)-cycloalkyl or 5- or 6-membered heterocyclyl; wherein (C.sub.1-C.sub.6)-alkyl is optionally up to trisubstituted by fluorine and up to disubstituted, identically or differently, by a radical selected from the group consisting of --OR.sup.18, --SR.sup.20, --NR.sup.21AR.sup.21B, (C.sub.3-C.sub.6)-cycloalkyl, 5- or 6-membered heterocyclyl and 5- or 6-membered heteroaryl; and wherein (i) the cycloalkyl groups are optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.3)-alkyl, hydroxyl, (C.sub.1-C.sub.3)-alkoxy, hydroxycarbonyl, methoxycarbonyl and ethoxycarbonyl; (ii) the heterocyclyl groups are optionally up to trisubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.3)-alkyl, hydroxyl, oxo, hydroxycarbonyl, methoxycarbonyl and ethoxycarbonyl; and (iii) the heteroaryl group is optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, (C.sub.1-C.sub.3)-alkyl and (C.sub.1-C.sub.3)-alkoxy; and wherein R.sup.18 is hydrogen, methyl or ethyl; R.sup.20 is methyl or ethyl; and R.sup.21A and R.sup.2lB are independently hydrogen, methyl or ethyl; or R.sup.8A and R.sup.8B are joined to one another and, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered heterocycle which optionally contains one further ring heteroatom selected from the group consisting of N and O, and which is optionally up to tetrasubstituted, identically or differently, by a radical selected from the group consisting of fluorine, (C.sub.1-C.sub.3)-alkyl, oxo, --OR.sup.23, --NR.sup.24AR.sup.24B and --C(.dbd.O)--NR.sup.25AR.sup.25B; wherein (C.sub.1-C.sub.3)-alkyl is optionally substituted by hydroxy or up to three times by fluorine; and wherein R.sup.23 is hydrogen or (C.sub.1-C.sub.3)-alkyl; wherein (C.sub.1-C.sub.3)-alkyl is optionally substituted by hydroxyl or up to trisubstituted by fluorine; and R.sup.24A, R.sup.24B, R.sup.25A and R.sup.25B are independently hydrogen, methyl or ethyl, or a salt, a solvate or a solvate of a salt thereof. 4. The compound of formula (I) according to claim 1, wherein: R.sup.1 is methyl; R.sup.2 is hydrogen; R.sup.3 is fluorine; and G is --CH.sub.2--NR.sup.8AR.sup.8B, wherein R.sup.8A is hydrogen, methyl or ethyl; and R.sup.8B is (C.sub.1-C.sub.6)-alkyl or (C.sub.3-C.sub.6)-cycloalkyl; wherein (C.sub.1-C.sub.6)-alkyl is optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of hydroxyl, methoxy and ethoxy; and (C.sub.3-C.sub.6)-cycloalkyl is optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of hydroxyl, methoxy, ethoxy, isopropoxy, hydroxycarbonyl, methoxycarbonyl and ethoxycarbonyl; or R.sup.8A and R.sup.8B are joined to one another and, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered heterocycle which optionally contains one further ring heteroatom selected from the group consisting of N and O, and which is optionally up to disubstituted, identically or differently, by a radical selected from the group consisting of methyl, ethyl, hydroxyl, methoxy, ethoxy and n-propoxy; wherein the methyl and ethyl are optionally substituted by hydroxyl, or a salt, a solvate or a solvate of a salt thereof. 5. A method for preparing the compound of formula (I) according to claim 1, wherein the compound of formula (I) is a compound of the formula (I-A), a compound of formula (I-B), a compound of formula (I-C) or a compound of formula (I-D), comprising: [A] reacting a compound of formula (II) ##STR00323## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; and PG.sup.1 is a suitable protecting group; in the presence of a base with 2,4-dichloropyridine-3-carboxylic acid (III) ##STR00324## to give a compound of formula (IV) ##STR00325## wherein PG.sup.1 is a suitable protecting group, and R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; coupling the compound of formula (IV) with 3,4-diaminobenzonitrile (V) ##STR00326## with activation of the carboxylic acid group in the compound of formula (IV) to give a compound of formula (VI) ##STR00327## wherein PG.sup.1 is a suitable protecting group, and R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; cyclizing the compound of formula (VI) by heating in an inert solvent to give a compound of formula (VII) ##STR00328## wherein PG.sup.1 is a suitable protecting group, and R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; and detaching the protecting group PG.sup.1 to obtain the compound of formula (I-A) ##STR00329## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; or [B] reacting a compound of formula (VIII) ##STR00330## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1, in the presence of an acid while heating with a compound of formula (IX) ##STR00331## to give the compound of formula (I-A) ##STR00332## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; and optionally [C] treating the compound of formula (I-A) with an aqueous acid to give the compound of formula (I-B) ##STR00333## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; and optionally coupling the compound of formula (I-B) with a compound of formula (X) ##STR00334## wherein R.sup.7A and R.sup.7B are as defined in claim 1; with activation of the carboxylic acid function in the compound of formula (I-B) to give the compound of formula (I-C) ##STR00335## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.7A and R.sup.7B are as defined in claim 1; or [D] reacting the compound of formula (I-A) with diisobutylaluminium hydride to give a compound of formula (XI) ##STR00336## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in claim 1; and reacting the compound of formula (XI) in the presence of a suitable reducing agent with a compound of formula (XII) ##STR00337## wherein R.sup.8A and R.sup.8B are as defined in claim 1; to give the compound of formula (I-D) ##STR00338## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.8A and R.sup.8B are as defined in claim 1; and the compound of formula (I-A), the compound of formula (I-B), the compound of formula (I-C) or the compound of formula (I-D) is optionally separated into its enantiomers or diastereomers, or optionally converted with the appropriate (i) solvent and/or (ii) acid or base to a solvate, a salt, or a solvate of a salt thereof. 6. A pharmaceutical composition comprising the compound of claim 1, or a salt, a solvate, or a solvate of a salt thereof, in combination with one or more inert, nontoxic, pharmaceutically suitable excipients. 7. A pharmaceutical composition comprising the compound of claim 1, or a salt, a solvate, or a solvate of a salt thereof, in combination with one or more VEGF signalling pathway inhibitors selected from the group consisting of aflibercept, ranibizumab, bevacizumab, and pegaptanib. 8. The method of claim 5, wherein PG.sup.1 is benzyl, 4-methoxybenzyl or 2,4-dimethoxybenzyl. 9. A pharmaceutical composition comprising the compound of claim 2, or a salt, a solvate, or a solvate of a salt thereof, in combination with one or more inert, nontoxic, pharmaceutically suitable excipients. 10. A pharmaceutical composition comprising the compound of claim 3, or a salt, a solvate, or a solvate of a salt thereof, in combination with one or more inert, nontoxic, pharmaceutically suitable excipients. 11. A pharmaceutical composition comprising the compound of claim 4, or a salt, a solvate, or a solvate of a salt thereof, in combination with one or more inert, nontoxic, pharmaceutically suitable excipients. 12. The compound of claim 1 or a salt thereof.

Details for Patent 10,047,096

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	February 26, 2004	10,047,096	2034-11-25
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	June 30, 2006	10,047,096	2034-11-25
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	August 10, 2012	10,047,096	2034-11-25
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	October 13, 2016	10,047,096	2034-11-25