# US 2015/0148522 A1 · Somatostatin-dopamine chimeric analogs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2015/0148522 A1 - Document ID: US20150148522A1 - Status: Published application - Kind: A1 - Application number: 14/614,458 - Filed: 2015-02-05 - Published: 2015-05-28 - Earliest claimed: 2012-11-01 - Assignees: Ipsen Pharma S.A.S. - Applicants: Ipsen Pharma S.A.S. - Inventors: Zheng Xin DONG; Yeelana SHEN - Web page: https://patentgrep.com/patent/US20150148522A1 ## CPC - A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 38/31: Somatostatins - A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 1/12: Antidiarrhoeals - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/04: Anorexiants; Antiobesity agents - A61P 3/06: Antihyperlipidemics - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/00: Drugs for disorders of the endocrine system - A61P 5/06: of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 13/08: of the prostate - A61P 13/12: of the kidneys - A61P 17/00: Drugs for dermatological disorders - A61P 19/00: Drugs for skeletal disorders - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/36: Opioid-abuse - A61P 27/02: Ophthalmic agents - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 37/02: Immunomodulators - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07C 215/52: linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring - C07K 14/655: Somatostatins - C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention relates to novel somatostatin-dopamine chimeric analogs and their therapeutic uses for the inhibition, prevention, and/or treatment of neoplasia, neuroendocrine tumors, Cushing's disease/syndrome, and other conditions. ## Claims ### Claim at position 1 1-2. (canceled) ### Claim 3 A method of treating a neuroendocrine tumor in a subject, said method comprising administering to said subject a therapeutically effective amount of a compound, wherein the compound is: (SEQ ID NO: 4) Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp- Lys-Thr-Phe); (SEQ ID NO: 5) Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-4FPhe); (SEQ ID NO: 6) Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys- Thr-4FPhe); (SEQ ID NO: 12) Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys- Thr-Tyr); (SEQ ID NO: 13) Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe- 4Pal-DTrp-Lys-Thr-Tyr); (SEQ ID NO: 14) Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe- 4Pal-DTrp-Lys-Thr-Phe); (SEQ ID NO: 15) Dop1(SO2)-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-4FPhe); (SEQ ID NO: 18) Dop1(SO)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp- Lys-Thr-Tyr); (SEQ ID NO: 19) Dop1(SO)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe- DTrp-Lys-Thr-4FPhe); (SEQ ID NO: 20) Dop1(SO)-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-4FPhe); (SEQ ID NO: 21) Dop1(SO)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal- DTrp-Lys-Thr-Phe); (SEQ ID NO: 22) Dop1(SO)-Lys[Dop1(SO)]-psi(CH2NH)-cyclo(DLys-Arg- Phe-4Pal-DTrp-Lys-Thr-Tyr); (SEQ ID NO: 23) Dop1(SO)-Lys[Dop1(S0)]-psi(CH2NH)-cyclo(DLys-Arg- Phe-4Pal-DTrp-Lys-Thr-Phe); (SEQ ID NO: 24) Dop1(SO2)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe- DTrp-Lys-Thr-4FPhe); (SEQ ID NO: 25) Dop1(SO2)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal- DTrp-Lys-Thr-Tyr); (SEQ ID NO: 26) Dop1(SO2)-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe- 4Pal-DTrp-Lys-Thr-Phe); (SEQ ID NO: 28) Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys- Thr-Phe); (SEQ ID NO: 29) Dop1-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Phe); (SEQ ID NO: 30) Dop1-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys-Thr-Tyr); (SEQ ID NO: 31) Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys- Thr-Phe); (SEQ ID NO: 35) bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-4Pal-DTrp- Lys-Thr-Phe); (SEQ ID NO: 39) Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-Phe); (SEQ ID NO: 40) Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-Tyr); (SEQ ID NO: 41) Dop1-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe); (SEQ ID NO: 42) bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-4Pal-DTrp- Lys-Thr-Tyr); (SEQ ID NO: 43) Dop1-DTyr-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr- Phe); (SEQ ID NO: 44) Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-3Pal-DTrp- Lys-Thr-Phe); (SEQ ID NO: 45) bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-4FPhe); (SEQ ID NO: 46) bis[Dop1-psi(CH2N)]-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-Phe); (SEQ ID NO: 47) Dop1-DTyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-Phe); (SEQ ID NO: 50) Dop1-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-Phe); (SEQ ID NO: 51) Dop1-DTyr-psi(CH2NH)-cyclo(DLys-Arg-4Pal-Tyr- DTrp-Lys-Thr-Phe); or (SEQ ID NO: 52) Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe- DTrp-Lys-Thr-4FPhe); or a pharmaceutically acceptable salt thereof, and wherein said therapeutically effective amount is the amount effective to treat said disease or disorder in said subject. ### Claim 4 (depends on 3) The method according claim 3, wherein said compound is: (SEQ ID NO: 4) Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp- Lys-Thr-Phe); (SEQ ID NO: 5) Dop1-Tyr-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-4FPhe); (SEQ ID NO: 6) Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys- Thr-4FPhe); (SEQ ID NO: 12) Dop1-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal-DTrp-Lys- Thr-Tyr); (SEQ ID NO: 13) Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal- DTrp-Lys-Thr-Tyr); (SEQ ID NO: 14) Dop1-Lys(Dop1)-psi(CH2NH)-cyclo(DLys-Arg-Phe-4Pal- DTrp-Lys-Thr-Phe); or (SEQ ID NO: 15) Dop1(SO2)-psi(CH2NH)-cyclo(DLys-Arg-Phe-Phe-DTrp- Lys-Thr-4FPhe); or a pharmaceutically acceptable salt thereof. ### Claim 5 (depends on 3) The method of claim 3, wherein said neuroendocrine tumor is a neuroendocrine tumor of the pituitary. ### Claim 6 (depends on 5) The method of claim 5, wherein said neuroendocrine tumor of the pituitary is an ACTH-producing tumor. ### Claim 7 (depends on 6) The method of claim 6, wherein the condition of said ACTH-producing tumor is Cushing's disease. ### Claim 8 (depends on 5) The method of claim 5, wherein said neuroendocrine tumor of the pituitary is a growth hormone producing tumor. ### Claim 9 (depends on 8) The method of claim 8, wherein the condition of said growth hormone producing tumor is acromegaly. ### Claim 10 (depends on 5) The method of claim 5, wherein said neuroendocrine tumor of the pituitary is a prolactin-producing tumor. ### Claim 11 (depends on 10) The method of claim 10, wherein the condition of said prolactin-producing tumor is a prolactinoma. ### Claim 12 (depends on 5) The method of claim 5, wherein said neuroendocrine tumor of the pituitary is hyperprolactinemia. ### Claim 13 (depends on 5) The method of claim 5, wherein said neuroendocrine tumor of the pituitary is thyroid stimulating hormone secreting tumor. ### Claim 14 (depends on 5) The method of claim 5, wherein said neuroendocrine tumor of the pituitary is “nonfunctioning” pituitary adenoma. ### Claim 15 (depends on 5) The method of claim 5, wherein said neuroendocrine tumor of the pituitary is gonadotropinoma. ### Claim 16 (depends on 3) The method of claim 3, wherein the neuroendocrine tumor is carcinoid tumor. ### Claim 17 (depends on 16) The method of claim 16, wherein said carcinoid tumor causes carcinoid syndrome. ### Claim 18 (depends on 3) The method of claim 3, wherein said neuroendocrine tumor is glucagonoma. ### Claim 19 (depends on 3) The method of claim 3, wherein said neuroendocrine tumor is small cell lung carcinoma. ### Claim 20 (depends on 3) The method of claim 3, wherein said neuroendocrine tumor is thyroid medullary carcinoma. ### Claim 21 (depends on 3) The method of claim 3, wherein said neuroendocrine tumor is VIPoma. ### Claim 22 (depends on 3) The method of claim 3, wherein said neuroendocrine tumor is insulinoma.