|
Patent landscape, scope, and claims: |
United States Patent 5,563,142: Scope, Claim Architecture, and US Patent Landscape for Diaromatic Substituted Diarginyl/Indole-Derived Piperazine Compounds
What is US 5,563,142’s claim scope in plain terms?
US 5,563,142 claims a family of “diaromatic substituted compounds” defined by a high-constraint core scaffold (labeled “compound (III)”) with extensive substitution permissiveness on multiple positions across two aromatic fragments and a central piperazine (or closely related N-containing ring system). The independent claim (claim 1) is a Markush-style construction that allows broad variation at multiple structural “handles,” while still binding to a tight set of chemical motifs and fragment-level definitions.
Independent claim 1 (breadth controls)
Claim 1 is directed to: a diaromatic substituted compound (III) of formula (III), with the following explicit degrees of freedom and constraints (condensed):
- R1: either –CH2– or –CO– (directly gates whether the core connector is methylene or carbonyl).
- Z: defined via a specific substructure (Z is constrained to the particular “##STR32##” moiety, not a free group).
- n12, n13: both set to 1 (hard constraint).
- Y3 / Y3-1: Y3 = –N(Y3-1)–, where Y3-1 = C1–C4 alkyl (N-substitution limited to short alkyl).
- R6: –N═ (fixed unsaturation motif).
- R7: –N(R7-5)(R7-6) with:
- R7-5: C1–C6 alkyl, or –CH2–cyclopropyl, or –CH2–CH2F
- R7-6: –H (forces mono-H at that nitrogen position).
- R8, R9, R10: each is a vinylidene-like / substituted double-bond fragment with substituent options only H or F:
- R8 = –CR8-1═
- R9 = –CR9-1═
- R10 = –CR10-1═
- R8-1, R9-1, R10-1 each = H or F
- Aryl/Heteroaryl substituent: selected from substituents of a separate “formula (7)” (constrained by that formula), including a double bond (“. . . . is a double bond” in the claim text).
- Q1: –NX11–, where X11 = H (N is NH, not N-alkyl at that handle).
- X14 region (multi-option amide/urea-like and imine/aminated variants):
- n7 = 0 or 1
- X6 options also appear later, but X14 governs a major functional branching.
- X14 is specified through multiple alternative chemistries including: H or O-CH2-phenyl, O-CH2-COOR14-10 (ester/alkoxycarbonyl with limited R choices), O-SO2-X, NO2, NH2, N3, NH-SO2-X, N═C(X14-4)–N(X14-7)(X14-8) (guanidine-like / amidine-like branch), and N(X14-2)-CO-X14-9 (amido-carbonyl branch).
- X6: H, OH, O-CH2-φ, CHO, C1–C3 alkoxy, O–SO2–X6-12, or C≡N (“--C.tbd.N”), or (CH2)n3–N(X6-3)(X6-4) where n3 = 2–5 and the terminal N can be part of a defined heterocycle:
- heterocycle choices: 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl, or 1-aziridinyl
- or n3–(CH2)n24–OH with n24 = 1
- or NH–SO2–X6-7 with X6-7 = C1–C4 alkyl
- Stereochemical/physical forms: claims include enantiomers and pharmaceutically acceptable salts, hydrates, and solvates.
Net effect: the claim permits large chemical variation, but each variation is tightly bounded to a controlled set of functional groups and substitution sizes (mostly C1–C6 alkyl, plus a defined fluorination allowance and fixed heterocycle/aryl substitution routes).
How do dependent claims narrow the scope?
Dependent claims progressively lock particular choices from claim 1 and then enumerate preferred “embodiments” that capture specific drug-like examples.
Key dependent-claim “tighteners”
- Claim 2: R1 = –CO– (selects carbonyl connector).
- Claim 3: Z = ##STR35## (locks Z to a particular variant).
- Claim 4: R7 is N(R7-5)(R7-6) where R7-5 = C1–C4 alkyl (narrows R7-5 from C1–C6 and other groups).
- Claim 5: C1–C4 alkyl further narrows to explicit isomers/structures:
- –CH2–CH3, –CH(CH3)2, –C(CH3)3
- Claims 6–8: define specific named compound list(s) that are literal embodiments of claim 1 with particular aryl/heteroaryl and amino substituents, plus a subset in claim 8.
- Claims 9–11: convert broad salt coverage into specific acid addition salt sets and then identify a single monomethanesulfonate salt.
What does the patent do with “example enumeration”?
Claims 6–8 include long explicit lists of compound names of the same general scaffold class. This has two legal-business consequences:
- It anchors the patent’s practical interpretation: even though claim 1 is Markush-defined, the patentee selected specific instantiations that can be used to map claimed structure to commercial candidates.
- It creates a usable “design-around map”: any competitor structure that diverges at those enumerated positions must be evaluated against the underlying claim formula rather than just the example list.
What are the explicit compound embodiments in claims 6–8?
Claims 6–8 list multiple specific compounds. The text provided includes many, dominated by indolyl (sometimes fluorinated/chlorinated/methoxylated/substituted) attached at the indole ring, coupled to a piperazine bearing a substituted pyridinyl and amino substituent.
Below is the structure pattern of the enumerated compounds as given (condensed into the claim’s own naming motifs), then specific items that appear in the claim text.
Common motif across the enumerated embodiments (from claim text)
- Indolyl-2-carbonyl (or indolyl-2-methyl) linked to
- 4-[3-(substituted amino)-2-pyridinyl]piperazine
The “substituted amino” group varies across ethylamino, propylamino, cyclopropylmethylamino, N,N-diethylamino, N,N-di-tert-butylamino, and other substituted amino groups. The indole ring varies by substitution: H/fluoro/chloro/bromo/methoxy/benzyloxy/ethoxycarbonylmethoxy/hydroxymethyl/cyano/nitro/azido/acetamido/methanesulfonamido/formyl/6-formyl, etc.
Examples explicitly named in the claim text
Examples include (verbatim naming patterns preserved):
- 1-[indolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine
- 1-[indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[indolyl-2-carbonyl]-4-[3-(N,N-diethylamino)-2-pyridinyl]piperazine
- 1-[indolyl-2-methyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine
- 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(propylamino)-2-pyridinyl]piperazine
- 1-[5-chloroindoyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piprazine (as written)
- 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine
- 1-[5-ethylindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine
- 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]-piperazine
- 1-[indolyl-2-carbonyl]-4-[3-(cyclopropylmethylamino)-2-pyridinyl]piperazine
- 1-[5-benzyloxyindolyl-2-carbonyl]-4-(3-ethylamino-2-pyridinyl)piperazine
- 1-[6-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[4-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-methylindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-fluoro-6-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-bromoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-bromo-6-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-aminoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-nitroindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-acetamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[6-formylindoyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-azido-2-indolycarbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[6-hydroxymethylindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-(6-cyanoindolyl-2-carbonyl)-4-[3-(ethylamino)-2-pyridinyl]piperazine
- 1-(6-cyanoindolyl-2-carbonyl)-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-[5-(N',N'-dimethylaminomethylene)aminoindolyl)carbonyl]-4-(3-(1-methylethylamino)-2-pyridinyl)piperazine) (as written with bracket mismatch)
- 1-[5-(ethoxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-(5-fluoroindolyl-2-carbonyl)-4-[3-methylamino-2-pyridinyl]piperazine
- 1-[5-(benzyloxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]-piperazine
- 1-[5-(carboxymethoxy)indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
- 1-(indolyl-2-carbonyl)-4-[3-(methylamino)-2-pyridinyl]piperazine
- 1-[5-(N-(N',N'-dimethylaminomethylene)aminoindolyl-2-carbonyl]-4-[3-(1,1-dimethylethylamino)-2-pyridinyl]piperazine
Claim 7 narrows to a subset from claim 6 (as written) that removes many of the more functionalized indoles and certain amino substitution patterns.
Claim 8 tightens to:
- 1-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine
How do the salt claims expand or constrain enforcement?
Claims 9–11 handle acid addition salts.
- Claim 9: salt is an acid addition salt.
- Claim 10: acid list includes:
- methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric
- benzoic, citric, tartaric, fumaric, maleic
- p-toluenesulfonic, benzenesulfonic
- CH3–(CH2)n–COOH where n = 0–4 (alkyl-substituted acids)
- HOOC–(CH2)n–COOH where n is as defined above
- Claim 11: locks to 1-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine monomethanesulfonate salt.
Business interpretation for landscape mapping
This salt layer is narrow for market defense because it identifies at least one specific salt. Still, the independent compound claim in claim 1 already covers “pharmaceutically acceptable salts” broadly. So competitors must evaluate both:
- whether they land inside the core scaffold under claim 1
- whether they still infringe even if they switch salt forms (claim 1 already includes salts, hydrates, solvates)
Where are the most infringement-sensitive structural “switches”?
From the written claim language, these switches likely drive claim coverage more than minor aromatic decoration:
- R1 connector: –CH2– vs –CO–
- Claim 2 forces –CO–, so a product with –CH2– is not covered by claim 2 but may still fall under claim 1.
- R7 nitrogen substitution pattern: R7-6 fixed to H; R7-5 restricted to specific sets
- Claim 4–5 tighten R7-5 to C1–C4 alkyl and then to specific isomers.
- Fluorination allowance at R8/R9/R10: each is H or F
- This enables multiple fluorinated variants without exiting the claim family.
- X6 aromatic substituent latitude: includes OH, alkoxy, sulfonyl, nitrile, and heterocycle-forming N-substituted linker options
- X6 can be used as a substitution “dial” for design-around; competitors must ensure their aryl substituents match none of the defined alternatives.
- Z identity and n12/n13: hard constraints
- If the competitor’s core Z (and ring topology encoded by n12/n13) differs, infringement drops quickly.
US patent landscape: what can be concluded from the provided inputs?
A complete US landscape for US 5,563,142 requires at least one of:
- the patent bibliographic data (assignee, filing date, publication data, continuation chain)
- citation lists (cited by/examined with)
- family members and prosecution history
- maintenance status and any reexamination/certainty
Those items are not present in the provided text. Under the analysis constraints, no further landscape assertions can be made without risking fabrication. What can be stated strictly from the claim text is the internal “landscape” of likely design-around and likely overlap zones based on the defined substitution parameters.
Practical “freedom map” for competitors (derived strictly from claim text)
Use the claim’s defined sets to classify competitor candidates:
| Structural element |
Allowed by claim 1 (as written) |
Typical design-around axis |
| R1 |
–CH2– or –CO– |
change connector type to something outside these two |
| N-substitution at Y3 |
N(Y3-1) with C1–C4 alkyl |
use N-substituents outside C1–C4 |
| R7 nitrogen |
N(R7-5)(H) with R7-5 in C1–C6 alkyl or specific groups |
use R7-5 outside list; change R7-6 away from H |
| R8/R9/R10 |
each H or F |
use other substituents at those positions |
| X11 |
H |
change the corresponding N to non-H substitution |
| X6 aromatic handle |
specific oxygen/sulfonyl/nitrile and heterocycle-forming linker options |
use substituents not enumerated for X6 |
| Salt forms |
pharmaceutically acceptable salts + claim 10 acid list |
choose a salt form still likely covered by claim 1 salts (but claim 11 is specific) |
Enforcement posture implied by claims 1 and 6–11
- Compound coverage is broad under claim 1 because it is written as a Markush-defined core formula with many allowed substituents.
- Claim 6’s enumeration helps map concrete embodiments (likely the commercially pursued structures) into the broader formula.
- Salt coverage in claims 9–11 provides layered protection: broad salts in claim 1 plus specific salts in dependent claims.
Key Takeaways
- US 5,563,142 claim 1 covers a large Markush family built on a constrained diaromatic scaffold with fixed ring-topology parameters (n12 = 1; n13 = 1) and a controlled substitution vocabulary across multiple positions.
- Dependent claims 2–5 narrow key chemical switches: R1 (–CO–), Z (specific variant), and R7-5 (C1–C4 alkyl) down to explicit alkyl isomers.
- Claims 6–8 list numerous specific indole/pyridine/piperazine embodiments, with claim 8 focusing on one specific methanesulfonamide-indole member.
- Claims 9–11 add salt-layer defense, with claim 10 enumerating common acid addition salts and claim 11 locking a specific monomethanesulfonate salt of the claim 8 compound.
- No external US patent landscape conclusions (other patents, citations, families, expiry, validity status) can be produced from the provided information; the analysis above is limited to the claim scope and the competition-meaning of the defined substituent sets.
FAQs
-
Is US 5,563,142’s main protection for a single molecule or a class?
It is a class-level protection via claim 1, which defines compound (III) with multi-position Markush alternatives plus coverage for enantiomers and pharmaceutically acceptable salts/hydrates/solvates.
-
Which claim elements most affect whether a candidate compound falls inside scope?
R1 (–CH2– vs –CO–), R7-5 and the fixed R7-6 = –H, fluorination allowances at R8/R9/R10 (only H or F), the identity of Z and fixed n12/n13 values, and the enumerated substitution options at X6.
-
Do the enumerated compounds in claim 6 expand the protection beyond claim 1?
They anchor specific embodiments within the broader formula. Scope still follows claim 1’s structure definition, not only the example list.
-
How do salt claims change infringement risk for generic salts?
Claim 1 already covers “pharmaceutically acceptable salts,” so switching among typical acid addition salts may not exit coverage. Claim 11 targets one specific monomethanesulfonate salt of a particular embodiment.
-
Can competitors design around by changing only minor substituents on the indole or pyridine rings?
Only if the new substituents fall outside the enumerated options defined for positions such as X6, and if other constrained handles (R7, R8/R9/R10, Z, n12/n13) are not preserved.
References
[1] United States Patent 5,563,142. Claims 1–11 (as provided in prompt text).
More… ↓
⤷ Start Trial
|
