DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-20 are pending in the instant invention.
Status of Priority
This invention is a Continuation (CON) of US Application No. 17/029,013, filed September 22, 2020 and now US 11,571,420, which is a Continuation (CON) of US Application No. 16/910,308, filed June 24, 2020 and now US 10,898,481, which is a Continuation (CON) of International Application No. PCT/CN2019/100996, filed August 16, 2019, which claims priority under 35 U.S.C. § 119(a-d) to International Application No. PCT/CN2016/101006, filed August 17, 2018.
Restrictions / Election of Species
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The inventor’s or joint inventor’s provisional election of the following, without traverse, in the reply filed on September 16, 2025, is acknowledged: a) Group I - claims 1-20; and b) substituted pyrazine of Formula (I) - p. 237, Example/Cmpd No. 151/152, shown to the right below, and hereafter referred to as 3-amino-N-(3-methoxycyclobutyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide, where m = 1; n = 0; ring A = -imidazo[1,2-a]pyridin-6-yl; at C-3, R1 = -CH3; ring B = -oxazol-2-yl; X = -NH2; W = -C(O)-; V = -NH-; and Y = -cyclobutyl, substituted at C-3 with R3, wherein R3 = -OCH3. Claims 1-5, 7, 8, 12-15, 19 and 20 read on the elected species. Affirmation of this election must be made by the inventor or joint inventor in replying to this Office action.
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Similarly, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
Moreover, the inventor or joint inventor should further note that the elected species, shown to the right, was found to be free of the prior art. Thus, the examiner has expanded the forthcoming prosecution to include all claims relevant to the genus of Group I, for a first Office action and prosecution on the merits.
Thus, a first Office action and prosecution on the merits of claims 1-20 is contained within.
Specification Objection - Disclosure
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(c). Revisions should particularly address bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Specification Objection - Title
The inventor or joint inventor is reminded of the proper content of the title of the invention.
The title of the invention should be brief, but technically accurate and descriptive and should contain fewer than 500 characters. See 37 CFR 1.72(a) and MPEP § 606.
The title of the invention is not technically accurate and descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. In the revised title, the examiner suggests additionally identifying a particular utility for the substituted pyrazines of the Formula (I).
The following title is suggested: SUBSTITUTED PYRAZINES FOR THE TREATMENT OF ADENOSINE RECEPTOR ASSOCIATED DISEASES.
Appropriate correction is required.
Specification Objection - Abstract
The inventor or joint inventor is reminded of the proper content of an abstract of the disclosure.
With regard particularly to chemical patents, for compounds or compositions, the general nature of the compound or composition should be given as well as the use thereof, e.g., The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics. Exemplification of a species could be illustrative of members of the class. For processes, the reactions, reagents and process conditions should be stated, generally illustrated by a single example, unless variations are necessary. See MPEP § 608.01(b), Section B.
The abstract of the disclosure is objected to because it fails to exemplify any members or formulae illustrative of its class. Correction is required. See MPEP § 608.01(b).
The examiner suggests incorporating the structure of Formula (I) into the abstract, to overcome this objection.
Claim Objections
Claim 1 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation(s):
1. A method for inhibiting adenosine receptor (AR) activity in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of Formula (I):
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Formula (I)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
ring A is morpholinyl, pyridinyl, pyridazinyl, pyridazin-3(2H)-onyl, pyrimidinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, benzo[d]imidazolyl, benzo[d]thiazolyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, or quinoxalinyl;
each R1 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, and OC1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl and saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
m is 0, 1, 2, 3, or 4;
ring B is a saturated or unsaturated 5- or 6-membered carbocyclyl or a saturated or unsaturated 5- or 6-membered heterocyclyl, wherein the heterocyclyl contains 1, 2, or 3 heteroatoms independently selected from the group consisting of N and O;
each R2 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, and OC1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl and saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R5 substituents;
each R5 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
n is 0, 1, 2, 3, or 4;
X is NH2;
W is C1-12 alkylene or -C(O)-, wherein the C1-12 alkylene is optionally substituted by one or more substituents independently selected from the group consisting of OH and OC1-12 alkyl;
V is -NH-, -NHC1-12 alkylene-, -NHC(O)-, or pyrrolidin-1-yl;
wherein any -NH- is optionally substituted by one substituent selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl;
wherein the C1-12 alkylene of -NHC1-12 alkylene- is optionally substituted by one or more substituents independently selected from the group consisting of NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl; and
wherein the pyrrolidin-1-yl is optionally substituted by one or more substituents independently selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl;
Y is halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 cyanoalkyl, C1-12 hydroxyalkyl, C(O)R3, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)C1-12 alkyl, OC(O)NH2, S(O)2R3, saturated or unsaturated 3- to 12-membered carbocyclyl, or saturated or unsaturated 3- to 12-membered heterocyclyl;
wherein the C1-12 alkyl, C1-12 haloalkyl, C1-12 cyanoalkyl, C1-12 hydroxyalkyl, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, or OC(O)C1-12 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, and saturated or unsaturated 3- to 10-membered heterocyclyl; and
wherein the saturated or unsaturated 3- to 12-membered carbocyclyl or saturated or unsaturated 3- to 12-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents;
each R3 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, and S(O)2C1-12 alkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each NHC3-12 cycloalkyl, NHC(O)NH2, OC(O)NH2, and OP(O)(OH)2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R6 substituents; and
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents.
21. A method for inhibiting adenosine receptor (AR) activity in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound of Formula (I):
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Formula (I)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
ring A is morpholinyl, pyridinyl, pyridazinyl, pyridazin-3(2H)-onyl, pyrimidinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, benzo[d]imidazolyl, benzo[d]thiazolyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, or quinoxalinyl;
each R1 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, and OC1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl and saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
m is 0, 1, 2, 3, or 4;
ring B is a saturated or unsaturated 5- or 6-membered carbocyclyl or a saturated or unsaturated 5- or 6-membered heterocyclyl, wherein the heterocyclyl contains 1, 2, or 3 heteroatoms independently selected from the group consisting of N and O;
each R2 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, and OC1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl and saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R5 substituents;
each R5 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
n is 0, 1, 2, 3, or 4;
X is NH2;
W is C1-12 alkylene or -C(O)-, wherein the C1-12 alkylene is optionally substituted by one or more substituents independently selected from the group consisting of OH and OC1-12 alkyl;
V is -NH-, -NHC1-12 alkylene-, -NHC(O)-, or pyrrolidin-1-yl;
wherein any -NH- is optionally substituted by one substituent selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl;
wherein the C1-12 alkylene of -NHC1-12 alkylene- is optionally substituted by one or more substituents independently selected from the group consisting of NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl; and
wherein the pyrrolidin-1-yl is optionally substituted by one or more substituents independently selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl;
Y is halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 cyanoalkyl, C1-12 hydroxyalkyl, C(O)R3, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)C1-12 alkyl, OC(O)NH2, S(O)2R3, saturated or unsaturated 3- to 12-membered carbocyclyl, or saturated or unsaturated 3- to 12-membered heterocyclyl;
wherein the C1-12 alkyl, C1-12 haloalkyl, C1-12 cyanoalkyl, C1-12 hydroxyalkyl, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, or OC(O)C1-12 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, and saturated or unsaturated 3- to 10-membered heterocyclyl; and
wherein the saturated or unsaturated 3- to 12-membered carbocyclyl or saturated or unsaturated 3- to 12-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents;
each R3 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, and S(O)2C1-12 alkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each NHC3-12 cycloalkyl, NHC(O)NH2, OC(O)NH2, and OP(O)(OH)2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R6 substituents; and
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, NH2, OH, OC1-12 alkyl, or OC1-12 haloalkyl;
m is 0, 1, or 2;
ring B is pyrrolidinyl, tetrahydrofuranyl, morpholinyl, phenyl, pyrrolyl, furanyl, pyrazolyl, imidazolyl, oxazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, or pyridinyl;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, CH2OH, CH(OHCH3, CH2CH2OH, NH2, NHCH3, N(CH3)2, NHCH2CH3, NHCH(CH3)2, OH, OCH3, OCH2CH3, OCHF2, or OCF3, wherein each C1-12 alkyl and C1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OC1-12 alkyl, and OC1-12 haloalkyl; and
n is 0, 1, or 2.
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein:
W is -CH2- or -C(O)-; or
(i) W is -CH2-; and
V is -NHC(O)-; or
(ii) W is -C(O)-; and
V is -NH-, -NHC1-12 alkylene-, or pyrrolidin-1-yl;
wherein the -NH- is optionally substituted by one substituent selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, OH, and OC1-12 alkyl;
wherein the C1-12 alkylene of -NHC1-12 alkylene- is optionally substituted by one or more substituents independently selected from the group consisting of OH and OC1-12 alkyl; and
wherein the pyrrolidin-1-yl is optionally substituted by one or more substituents independently selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, OH, and OC1-12 alkyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 4 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein Y is CN, C1-12 alkyl, C1-12 hydroxyalkyl, C(O)R3, NH2, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, S(O)2R3, saturated or unsaturated 3- to 12-membered carbocyclyl, or saturated or unsaturated 3- to 12-membered heterocyclyl;
wherein the C1-12 alkyl, C1-12 hydroxyalkyl, NH2, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, or OC1-12 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, and saturated or unsaturated 3- to 10-membered heterocyclyl; and
wherein the saturated or unsaturated 3- to 12-membered carbocyclyl or saturated or unsaturated 3- to 12-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 5 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein each R3 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2NH2, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH2CH3, NHcyclobutyl, OH, OCH3, OCH2CH3, OCH(OH)CH3, OCH2CH2OH, PH2, P(O)(OH)3, S(O)2CH3, cyclopropyl, cyclobutyl, cyclohexyl, azetidinyl, pyrrolidinyl, piperidinyl, pyranyl, piperazinyl, morpholinyl, 1,4-dioxanyl, bicyclo[1.1.1]pentanyl, 1,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3,8-diazabicyclo[3.2.1]octanyl, phenyl, furanyl, pyridinyl, or pyrazinyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2NH2, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH2CH3, OH, OCH3, OCH2CH3, PH2, P(O)(OH)3, and S(O)2CH3 is optionally and independently substituted by one or more substituents independently selected from the group consisting of F, C(O)NH2, C(O)NHCH3, C(O)N(CH3)2, NH2, NHCH3, N(CH3)2, OH, OCH3, OCH2CH3, S(O)2CH3, and cyclopropyl; and
wherein each NHcyclobutyl, cyclopropyl, cyclobutyl, cyclohexyl, azetidinyl, pyrrolidinyl, piperidinyl, pyranyl, piperazinyl, morpholinyl, 1,4-dioxanyl, bicyclo[1.1.1]pentanyl, 1,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3,8-diazabicyclo[3.2.1]octanyl, phenyl, furanyl, pyridinyl, and pyrazinyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, C(O)NHCH3, C(O)N(CH3)2, NH2, NHCH3, N(CH3)2, OH, OCH3, OCH2CH3, S(O)2CH3, and cyclopropyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is independently substituted by one or more independently selected C1-12 alkyl substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ia):
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Formula (Ia)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, NH2, or OH, wherein each C1-12 alkyl, C1-12 haloalkyl, NH2, and OH is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OH, OC1-12 alkyl, and OC1-12 haloalkyl;
(i) Z is a bond; and
Y is C(O)R3, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OC1-12 alkyl, OC1-12 haloalkyl, S(O)2R3, saturated or unsaturated 3- to 6-membered carbocyclyl, or saturated or unsaturated 3- to 6-membered heterocyclyl;
wherein the NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OC1-12 alkyl, or OC1-12 haloalkyl, is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, and saturated or unsaturated 3- to 10-membered heterocyclyl; and
wherein the saturated or unsaturated 3- to 6-membered carbocyclyl or saturated or unsaturated 3- to 6-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents; or
(ii) Z is C1-12 alkylene; and
Y is halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 6-membered carbocyclyl, and saturated or unsaturated 3- to 6-membered heterocyclyl; and
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is substituted by one or more independently selected C1-12 alkyl substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 7, wherein:
(i) Z is a bond; and
Y is cyclobutyl, wherein the cyclobutyl is substituted by one OC1-12 alkyl substituent and optionally further substituted by one or more OCH3 substituents; or
(ii) Z is -CH2CH2-; and
Y is OCH3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ia-i):
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Formula (Ia-i)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, NH2, OH, OC1-12 alkyl, or OC1-12 haloalkyl;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, NH2, or OH, wherein each C1-12 alkyl, C1-12 haloalkyl, NH2, and OH is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OH, OC1-12 alkyl, and OC1-12 haloalkyl;
R7 is H, C1-11 alkyl, C1-11 hydroxyalkyl, or OC1-12 alkyl;
ring Q is a saturated or unsaturated 3- to 6-membered carbocyclyl or a saturated or unsaturated 3- to 6-membered heterocyclyl;
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is substituted by one or more independently selected C1-12 alkyl substituents; and
i is 0, 1, 2, 3, or 4.
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ib):
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Formula (Ib)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, NH2, OH, OC1-12 alkyl, or OC1-12 haloalkyl;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, NH2, or OH, wherein each C1-12 alkyl, C1-12 haloalkyl, NH2, and OH is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OH, OC1-12 alkyl, and OC1-12 haloalkyl;
R7 is H, C1-11 alkyl, C1-11 hydroxyalkyl, or OC1-12 alkyl;
ring Q is a saturated or unsaturated 3- to 6-membered carbocyclyl or a saturated or unsaturated 3- to 6-membered heterocyclyl;
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is substituted by one or more independently selected C1-12 alkyl substituents; and
i is 0, 1, 2, 3, or 4.
Appropriate correction is required. See MPEP § 2173.02.
Claim 11 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 10, wherein:
each R1 is independently F, Cl, CH3, CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CH(OH)CH3, CH2CH2OH, NH2, cyclopropyl, or oxetanyl;
m is 0, 1, or 2;
ring B is phenyl, furanyl, pyrazolyl, oxazolyl, or 2H-1,2,3-triazolyl;
each R2 is independently F or CH3;
n is 0 or 1;
ring Q is cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, phenyl, pyrazolyl, thiazolyl, pyridinyl, or pyrimidinyl;
each R3 is independently F, Cl, Br, CN, CH3, CH2F, CHF2, CF3, CH2OH, CH2P(CH3)2, CH2CH3, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHCH(CH3)2, NHCH(OH)CH3, NHCH2CH2OH, N(CH3)2, OCH3, OCHF2, OCF3, OCH2C(O)NH2, OCH2CH3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OCH(OH)CH3, OCH2CH2OH, OCH(NHCH3)CH3, OCH2CH2NHCH3, OCH[N(CH3)2]CH3, OCH2CH2N(CH3)2, OCH(OCH3)CH3, OCH2CH2OCH3, azetidinyl, azetidinyl-N(CH3)2, pyrrolidinyl, morpholinyl, 5-methyl-2,5-diazaspiro[3.3]heptan-2-yl, 6-methyl-2,6-diazaspiro[3.4]octan-2-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptanyl, 3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl, pyrazinyl, or N-methylpyrazinyl; and
i is 0, 1, 2, or 3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 12 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ia-ii):
PNG
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200
400
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Greyscale
Formula (Ia-ii)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, C1-12 alkyl, CH2F, CHF2, CF3, CH2OH, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCF3, OCH2CH3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each C1-12 alkyl, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substitu