➤ Get the DrugPatentWatch Daily Briefing

Get Daily Updates on Generic Entry, Litigation, Biosimilars, and more …

Serving leading biopharmaceutical companies globally:

Merck
Johnson and Johnson
Moodys
Medtronic
McKesson
Dow

Last Updated: July 12, 2020

DrugPatentWatch Database Preview

Claims for Patent: 9,399,627

» See Plans and Pricing

« Back to Dashboard

Summary for Patent: 9,399,627
Title:Substituted macrocyclic compounds having proteasome inhibitory activity
Abstract: The disclosure provides for novel compounds which have proteasome inhibitory activity, pharmaceutical compositions made thereof, and methods of use thereof to treat various disorders, including cancer and nonmalignant tumors.
Inventor(s): Pirrung; Michael C. (Riverside, CA)
Assignee: The Regents of the University of California (Oakland, CA)
Application Number:14/408,140
Patent Claims:1. A compound having a structure of Formula II(a): ##STR00028## or a pharmaceutically acceptable salt thereof, wherein: X is NH, A.sup.1-A.sup.4 are each independently selected from hydrogen, deuterium, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkenyl, (C.sub.1-C.sub.6)alkynyl, (C.sub.1-C.sub.5)hetero-alkyl, (C.sub.1-C.sub.5)hetero-alkenyl, and (C.sub.1-C.sub.5)hetero-alkynyl; A.sup.6-A.sup.8 are each independently selected from hydrogen, deuterium, hydroxyl, halo, cyano, amino, nitro, alkoxy, alkoxycarbonyl, (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.4)alkenyl, (C.sub.1-C.sub.4)alkynyl, (C.sub.1-C.sub.3)hetero-alkyl, (C.sub.1-C.sub.3)hetero-alkenyl, and (C.sub.1-C.sub.3)hetero-alkynyl; A.sup.12 is selected from hydrogen, deuterium, hydroxyl, halo, cyano, amino, carboxamido, carboxyl, nitro, alkoxy, alkoxycarbonyl, (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkenyl, (C.sub.1-C.sub.8)alkynyl, (C.sub.1-C.sub.7)hetero-alkyl, (C.sub.1-C.sub.7)hetero-alkenyl, (C.sub.1-C.sub.7)hetero-alkynyl, cycloalkyl, aryl, and heterocycle; A.sup.13 is selected from hydrogen, deuterium, hydroxyl, halo, cyano, amino, carboxamido, carboxyl, nitro, alkoxy, alkoxycarbonyl, (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.4)alkenyl, (C.sub.1-C.sub.4)alkynyl, (C.sub.1-C.sub.3)hetero-alkyl, (C.sub.1-C.sub.3)hetero-alkenyl, (C.sub.1-C.sub.3)hetero-alkynyl, cycloalkyl, aryl, and heterocycle; and A.sup.14 is selected from hydrogen, deuterium, (C.sub.12-C.sub.16)alkyl, (C.sub.12-C.sub.16)alkenyl, (C.sub.12-C.sub.16)alkynyl, (C.sub.12-C.sub.15)hetero-alkyl, (C.sub.12-C.sub.15)hetero-alkenyl, (C.sub.12-C.sub.15)hetero-alkynyl, cycloalkyl, aryl, and heterocycle, wherein the heteroatoms making up the hetero-alkyl, hetero-alkenyl, hetero-alkynyl, and heterocycle are selected from N, O and/or S.

2. The compound of claim 1, wherein the compound is selected from: ##STR00029## ##STR00030## ##STR00031## or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1, comprising a structure of Formula II(b): ##STR00032## or a pharmaceutically acceptable salt thereof, wherein: X is NH; A.sup.14 is selected from hydrogen, deuterium, (C.sub.12-C.sub.16)alkyl, (C.sub.12-C.sub.16)alkenyl, (C.sub.12-C.sub.16)alkynyl, (C.sub.12-C.sub.15)hetero-alkyl, (C.sub.12-C.sub.15)hetero-alkenyl, (C.sub.12-C.sub.15)hetero-alkynyl, cycloalkyl, aryl, and heterocycle, wherein the heteroatoms making up the hetero-alkyl, hetero-alkenyl, hetero-alkynyl, and heterocycle are selected from N, O and/or S.

4. The compound of claim 3, wherein the compound is selected from: ##STR00033## or a pharmaceutically acceptable salt thereof.

5. A compound having the structure of: ##STR00034## or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising the compound of claim 1 and one or more pharmaceutically acceptable carriers.

7. The pharmaceutical composition of claim 6, wherein the composition is formulated to be administered intravenously or subcutaneously.

8. The pharmaceutical composition of claim 7, wherein the intravenous or subcutaneously dose comprises between 1 mg/mL to 5 mg/mL of the compound.

9. A method of treating a subject having or suspected of having a cancer comprising administering a therapeutically effective amount of the compound of claim 1 to the subject in need thereof, wherein the subject has a cancer selected from the group consisting of ovarian cancer, breast cancer, colorectal cancer, colon cancer, rectal cancer, prostate cancer, kidney or renal cancer, CNS neoplasms, neuroblastomas, glioblastomas, melanomas, non-small cell lung cancer and leukemia.

10. The method of claim 9, wherein the cancer is kidney cancer.

11. The method of claim 9, further comprising the administration of one or more additional therapeutic agents.

12. The method of claim 11, wherein the one or more additional therapeutic agents are one or more chemotherapeutic agents.

13. The method of claim 12, wherein the one or more chemotherapeutic agents is selected from cisplatin, carboplatin, vinblastine, platinum, arginine deiminase, asparaginase, thiotepa, cyclosphosphamide, busulfan, improsulfan, piposulfan, calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone, aminoglutethimide, mitotane, trilostane, flutamide, nilutamide, bicalutamide, leuprolide, goserelin, aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, calicheamicin, carabicin, caminomycin, carzinophilin, chromomycins, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin, tamoxifen, raloxifene, 4-hydroxytamoxifen, trioxifene, keoxifene, LY 117018, onapristone, toremifene, methotrexate, 5-fluorouracil, denopterin, methotrexate, pteropterin, trimetrexate, benzodopa, carboquone, meturedopa, uredopa, ethylenimines, altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide, trimethylolomelamine, frolinic acid, chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard, carmustine, chlorozotocin, fotemustine, lomustine, nimustine, ranimustine, fludarabine, 6-mercaptopurine, thiamiprine, thioguanine, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, paclitaxel, docetaxel, RFS 2000, thymidylate synthase inhibitors, aceglatone, aldophosphamide glycoside, aminolevulinic acid, amsacrine, bestrabucil, bisantrene, edatraxate, defofamine, demecolcine, diaziquone, difluoromethylornithine (DMFO), elformithine, elliptinium acetate, etoglucid, gallium nitrate, hydroxyurea, lentinan, lonidamine, mitoguazone, mitoxantrone, mopidamol, nitracrine, pentostatin, phenamet, pirarubicin, podophyllinic acid, 2-ethylhydrazide, procarbazine, razoxane, sizofuran, spirogermanium, tenuazonic acid, triaziquone, 2,2',2''-trichlorotriethylamine, urethane, vindesine, dacarbazine, mannomustine, mitobronitol, mitolactol, pipobroman, gacyto sine, arabinoside ("Ara-C"), chlorambucil, gemcitabine, 6-thioguanine, mercaptopurine, methotrexate, etoposide, ifosfamide, mitomycin C, mitoxantrone, vincristine, vinorelbine, navelbine, novantrone, teniposide, daunomycin, aminopterin, xeloda, ibandronate, CPT-11, retinoic acid, esperamicins, and capecitabine.

14. The method of claim 12, wherein the one or more chemotherapeutic agents is selected from vinblastine, floxuridine, 5-fluorouracil, capecitabine, gemcitabine, bortezomib, cyclophosphamide, melphalan, doxorubicin, idarubicin, cisplatin, etoposide, and bendamustine.

15. The compound of claim 1, wherein the compound has a structure of Formula II(a): ##STR00035## or a pharmaceutically acceptable salt thereof, wherein: X is NH; A.sup.1-A.sup.4, A.sup.6-A.sup.8, A.sup.12 are hydrogen; A.sup.13 is a 1-hydroxyethyl group; and A.sup.14 is a (C.sub.12-C.sub.16)alkenyl group.

Summary for Patent:   Start Trial

PCT Information
PCT FiledJune 14, 2013PCT Application Number:PCT/US2013/045854
PCT Publication Date:December 19, 2013PCT Publication Number:WO2013/188750

Details for Patent 9,399,627

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Merck ELSPAR asparaginase VIAL 101063 001 1978-01-10   Start Trial The Regents of the University of California (Oakland, CA) 2032-06-15 RX search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

Make Better Decisions: Try a trial or see plans & pricing

Serving leading biopharmaceutical companies globally:

Moodys
McKesson
Johnson and Johnson
Baxter
Boehringer Ingelheim
Medtronic

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.